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  • In the news: The Lasker goes to Michael Hall
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Kim Baumann

    In the news: The Lasker goes to Michael HallNature Reviews Molecular Cell Biology, Published online: 21 September 2017; doi:10.1038/nrm.2017.97The 2017 Albert Lasker Basic Medical Research Award was awarded to Michael N. Hall (Biozentrum, University of Basel, Switzerland) “for discoveries concerning the nutrient-activated TOR proteins and their central role in the metabolic control of cell growth”.

    更新日期:2017-09-21
  • Ubiquitylation at the crossroads of development and disease
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-20
    Michael Rape

    Human development requires intricate cell specification and communication pathways that allow an embryo to generate and appropriately connect more than 200 different cell types. Key to the successful completion of this differentiation programme is the quantitative and reversible regulation of core signalling networks, and post-translational modification with ubiquitin provides embryos with an essential tool to accomplish this task. Instigated by E3 ligases and reversed by deubiquitylases, ubiquitylation controls many processes that are fundamental for development, such as cell division, fate specification and migration. As aberrant function or regulation of ubiquitylation enzymes is at the roots of developmental disorders, cancer, and neurodegeneration, modulating the activity of ubiquitylation enzymes is likely to provide strategies for therapeutic intervention.

    更新日期:2017-09-21
  • Chromosome biology: Different turfs for cohesin and condensin
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-23
    Eytan Zlotorynski

    In yeast, mitotic chromosome condensation is achieved by cis-chromatin looping, a process in which cohesin and condensin have distinct roles.

    更新日期:2017-09-21
  • Genome editing: CRISPR–Cas becoming more human
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Kim Baumann

    CRISPR–Cas9 was used in human embryos to correct a dominant heterozygous gene mutation that causes hypertrophic cardiomyopathy.

    更新日期:2017-09-21
  • Nuclear Envelope: Chromosomes: one BAF layer to bind them all
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Paulina Strzyz

    Barrier-to-autointegration factor (BAF) forms a layer on the surface of chromatin at late mitosis, guiding the reformation of a single nuclear envelope surrounding all chromosomes.

    更新日期:2017-09-21
  • Cell organization by liquid phase separation
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Daniel W. Gerlich

    Daniel Gerlich discusses how a study by the Hyman laboratory introduced the theory of liquid phase separation to cell biology and its implications for the understanding of cell organization and function.

    更新日期:2017-09-21
  • Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Nard Kubben, Tom Misteli

    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson–Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

    更新日期:2017-09-21
  • In the news: The Lasker goes to Michael Hall
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-21
    Kim Baumann

    The 2017 Albert Lasker Basic Medical Research Award was awarded to Michael N. Hall (Biozentrum, University of Basel, Switzerland) “for discoveries concerning the nutrient-activated TOR proteins and their central role in the metabolic control of cell growth”.

    更新日期:2017-09-21
  • Cancer biology: The skin's power of elimination
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Paulina Strzyz

    The skin is able to counteract tissue aberrancies resulting from tissue overgrowth and to restore normal tissue architecture by eliminating aberrant cells.

    更新日期:2017-09-21
  • The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-05
    Arnab Ray Chaudhuri, André Nussenzweig

    Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers. Understanding the role of PARP1 in maintaining genome integrity is not only important for the design of novel chemotherapeutic agents, but is also crucial for gaining insights into the mechanisms of chemoresistance in cancer cells. In this Review, we discuss the roles of PARP1 in mediating various aspects of DNA metabolism, such as single-strand break repair, nucleotide excision repair, double-strand break repair and the stabilization of replication forks, and in modulating chromatin structure.

    更新日期:2017-09-21
  • The essential kinase ATR: ensuring faithful duplication of a challenging genome
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Joshua C. Saldivar, David Cortez, Karlene A. Cimprich

    One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. We discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. This involves a core set of components that recruit ATR to stressed replication forks, stimulate kinase activity and amplify ATR signalling. We focus on the activities of ATR in the control of cell cycle checkpoints, origin firing and replication fork stability, and on how proper regulation of these processes is crucial to ensure faithful duplication of a challenging genome.

    更新日期:2017-09-21
  • Splicing and transcription touch base: co-transcriptional spliceosome assembly and function
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Lydia Herzel, Diana S. M. Ottoz, Tara Alpert, Karla M. Neugebauer

    Several macromolecular machines collaborate to produce eukaryotic messenger RNA. RNA polymerase II (Pol II) translocates along genes that are up to millions of base pairs in length and generates a flexible RNA copy of the DNA template. This nascent RNA harbours introns that are removed by the spliceosome, which is a megadalton ribonucleoprotein complex that positions the distant ends of the intron into its catalytic centre. Emerging evidence that the catalytic spliceosome is physically close to Pol II in vivo implies that transcription and splicing occur on similar timescales and that the transcription and splicing machineries may be spatially constrained. In this Review, we discuss aspects of spliceosome assembly, transcription elongation and other co-transcriptional events that allow the temporal coordination of co-transcriptional splicing.

    更新日期:2017-09-21
  • Nuclear Envelope: Chromosomes: one BAF layer to bind them all
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Paulina Strzyz

    Nuclear Envelope: Chromosomes: one BAF layer to bind them allNature Reviews Molecular Cell Biology, Published online: 6 September 2017; doi:10.1038/nrm.2017.96Barrier-to-autointegration factor (BAF) forms a layer on the surface of chromatin at late mitosis, guiding the reformation of a single nuclear envelope surrounding all chromosomes.

    更新日期:2017-09-12
  • Fluorescence nanoscopy in cell biology
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Steffen J. Sahl, Stefan W. Hell, Stefan Jakobs

    Fluorescence nanoscopy uniquely combines minimally invasive optical access to the internal nanoscale structure and dynamics of cells and tissues with molecular detection specificity. While the basic physical principles of 'super-resolution' imaging were discovered in the 1990s, with initial experimental demonstrations following in 2000, the broad application of super-resolution imaging to address cell-biological questions has only more recently emerged. Nanoscopy approaches have begun to facilitate discoveries in cell biology and to add new knowledge. One current direction for method improvement is the ambition to quantitatively account for each molecule under investigation and assess true molecular colocalization patterns via multi-colour analyses. In pursuing this goal, the labelling of individual molecules to enable their visualization has emerged as a central challenge. Extending nanoscale imaging into (sliced) tissue and whole-animal contexts is a further goal. In this Review we describe the successes to date and discuss current obstacles and possibilities for further development.

    更新日期:2017-09-12
  • The emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Paul Schimmel

    The discovery of the genetic code and tRNAs as decoders of the code transformed life science. However, after establishing the role of tRNAs in protein synthesis, the field moved to other parts of the RNA world. Now, tRNA research is blooming again, with demonstration of the involvement of tRNAs in various other pathways beyond translation and in adapting translation to environmental cues. These roles are linked to the presence of tRNA sequence variants known as isoacceptors and isodecoders, various tRNA base modifications, the versatility of protein binding partners and tRNA fragmentation events, all of which collectively create an incalculable complexity. This complexity provides a vast repertoire of tRNA species that can serve various functions in cellular homeostasis and in adaptation of cellular functions to changing environments, and it likely arose from the fundamental role of RNAs in early evolution.

    更新日期:2017-09-12
  • Cell organization by liquid phase separation
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Daniel W. Gerlich

    Cell organization by liquid phase separationNature Reviews Molecular Cell Biology, Published online: 6 September 2017; doi:10.1038/nrm.2017.93Daniel Gerlich discusses how a study by the Hyman laboratory introduced the theory of liquid phase separation to cell biology and its implications for the understanding of cell organization and function.

    更新日期:2017-09-12
  • Cytosolic lipolysis and lipophagy: two sides of the same coin
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-30
    Rudolf Zechner, Frank Madeo, Dagmar Kratky

    Fatty acids are the most efficient substrates for energy production in vertebrates and are essential components of the lipids that form biological membranes. Synthesis of triacylglycerols from non-esterified free fatty acids (FFAs) combined with triacylglycerol storage represents a highly efficient strategy to stockpile FFAs in cells and prevent FFA-induced lipotoxicity. Although essentially all vertebrate cells have some capacity to store and utilize triacylglycerols, white adipose tissue is by far the largest triacylglycerol depot and is uniquely able to supply FFAs to other tissues. The release of FFAs from triacylglycerols requires their enzymatic hydrolysis by a process called lipolysis. Recent discoveries thoroughly altered and extended our understanding of lipolysis. This Review discusses how cytosolic 'neutral' lipolysis and lipophagy, which utilizes 'acid' lipolysis in lysosomes, degrade cellular triacylglycerols as well as how these pathways communicate, how they affect lipid metabolism and energy homeostasis and how their dysfunction affects the pathogenesis of metabolic diseases. Answers to these questions will likely uncover novel strategies for the treatment of prevalent metabolic diseases.

    更新日期:2017-09-12
  • Regulation of heat shock transcription factors and their roles in physiology and disease
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-30
    Rocio Gomez-Pastor, Eileen T. Burchfiel, Dennis J. Thiele

    The heat shock transcription factors (HSFs) were discovered over 30 years ago as direct transcriptional activators of genes regulated by thermal stress, encoding heat shock proteins. The accepted paradigm posited that HSFs exclusively activate the expression of protein chaperones in response to conditions that cause protein misfolding by recognizing a simple promoter binding site referred to as a heat shock element. However, we now realize that the mammalian family of HSFs comprises proteins that independently or in concert drive combinatorial gene regulation events that activate or repress transcription in different contexts. Advances in our understanding of HSF structure, post-translational modifications and the breadth of HSF-regulated target genes have revealed exciting new mechanisms that modulate HSFs and shed new light on their roles in physiology and pathology. For example, the ability of HSF1 to protect cells from proteotoxicity and cell death is impaired in neurodegenerative diseases but can be exploited by cancer cells to support their growth, survival and metastasis. These new insights into HSF structure, function and regulation should facilitate the development tof new disease therapeutics to manipulate this transcription factor family.

    更新日期:2017-09-12
  • Genome organization: A vision of 3D chromatin organization
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Kim Baumann

    Genome organization: A vision of 3D chromatin organizationNature Reviews Molecular Cell Biology, Published online: 23 August 2017; doi:10.1038/nrm.2017.88A new imaging technique (ChromEMT) enables the visualization of the local polymer structure and global 3D organization of chromatin in the nucleus of intact interphase and mitotic human cells.

    更新日期:2017-09-12
  • Chromosome biology: Different turfs for cohesin and condensin
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-23
    Eytan Zlotorynski

    Chromosome biology: Different turfs for cohesin and condensinNature Reviews Molecular Cell Biology, Published online: 23 August 2017; doi:10.1038/nrm.2017.90In yeast, mitotic chromosome condensation is achieved by cis-chromatin looping, a process in which cohesin and condensin have distinct roles.

    更新日期:2017-09-12
  • Cancer biology: The skin's power of elimination
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Paulina Strzyz

    The skin is able to counteract tissue aberrancies resulting from tissue overgrowth and to restore normal tissue architecture by eliminating aberrant cells.

    更新日期:2017-09-06
  • Genome editing: CRISPR–Cas becoming more human
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Kim Baumann

    CRISPR–Cas9 was used in human embryos to correct a dominant heterozygous gene mutation that causes hypertrophic cardiomyopathy.

    更新日期:2017-09-06
  • The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-05
    Arnab Ray Chaudhuri, André Nussenzweig

    Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers. Understanding the role of PARP1 in maintaining genome integrity is not only important for the design of novel chemotherapeutic agents, but is also crucial for gaining insights into the mechanisms of chemoresistance in cancer cells. In this Review, we discuss the roles of PARP1 in mediating various aspects of DNA metabolism, such as single-strand break repair, nucleotide excision repair, double-strand break repair and the stabilization of replication forks, and in modulating chromatin structure.

    更新日期:2017-09-06
  • Splicing and transcription touch base: co-transcriptional spliceosome assembly and function
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Lydia Herzel, Diana S. M. Ottoz, Tara Alpert, Karla M. Neugebauer

    Several macromolecular machines collaborate to produce eukaryotic messenger RNA. RNA polymerase II (Pol II) translocates along genes that are up to millions of base pairs in length and generates a flexible RNA copy of the DNA template. This nascent RNA harbours introns that are removed by the spliceosome, which is a megadalton ribonucleoprotein complex that positions the distant ends of the intron into its catalytic centre. Emerging evidence that the catalytic spliceosome is physically close to Pol II in vivo implies that transcription and splicing occur on similar timescales and that the transcription and splicing machineries may be spatially constrained. In this Review, we discuss aspects of spliceosome assembly, transcription elongation and other co-transcriptional events that allow the temporal coordination of co-transcriptional splicing.

    更新日期:2017-09-06
  • Mitochondrial diseases: the contribution of organelle stress responses to pathology
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Anu Suomalainen, Brendan J. Battersby

    Mitochondrial diseases affect one in 2,000 individuals; they can present at any age and they can manifest in any organ. How defects in mitochondria can cause such a diverse range of human diseases remains poorly understood. Insight into this diversity is emerging from recent research that investigated defects in mitochondrial protein synthesis and mitochondrial DNA maintenance, which showed that many cell-specific stress responses are induced in response to mitochondrial dysfunction. Studying the molecular regulation of these stress responses might increase our understanding of the pathogenesis and variability of human mitochondrial diseases.

    更新日期:2017-09-06
  • The essential kinase ATR: ensuring faithful duplication of a challenging genome
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Joshua C. Saldivar, David Cortez, Karlene A. Cimprich

    One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. We discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. This involves a core set of components that recruit ATR to stressed replication forks, stimulate kinase activity and amplify ATR signalling. We focus on the activities of ATR in the control of cell cycle checkpoints, origin firing and replication fork stability, and on how proper regulation of these processes is crucial to ensure faithful duplication of a challenging genome.

    更新日期:2017-09-06
  • Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Nard Kubben, Tom Misteli

    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson–Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

    更新日期:2017-09-06
  • Microtubule nucleation: beyond the template
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-23
    Johanna Roostalu, Thomas Surrey

    Microtubules are cytoskeletal filaments central to a wide range of essential cellular functions in eukaryotic cells. Consequently, cells need to exert tight control over when, where and how many microtubules are being made. Whereas the regulation of microtubule dynamics is well studied, the molecular mechanisms of microtubule nucleation are still poorly understood. Next to the established master template of nucleation, the γ-tubulin ring complex, other microtubule-associated proteins that affect microtubule dynamic properties have recently been found to contribute to nucleation. It has begun to emerge that the nucleation efficiency is controlled not only by template activity but also by, either additionally or alternatively, the stabilization of the nascent microtubule 'nucleus'. This suggests a simple conceptual framework for the mechanisms regulating microtubule nucleation in cells.

    更新日期:2017-09-06
  • Splicing: Phasing alternative exons
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-26
    Eytan Zlotorynski

    Two papers report a new mechanism of controlling alternative splicing through phase separation-mediated formation of higher-order assemblies of splicing factors.

    更新日期:2017-08-23
  • Epigenetics: Getting instructions from mum
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-02
    Paulina Strzyz

    Patterns of histone H3 Lys27 trimethylation are maternally inherited in both fly and mammalian embryos, and control gene expression during early development.

    更新日期:2017-08-23
  • Stress responses: SIRT1 puts an embargo on mRNA export
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Paulina Strzyz

    Sirtuin 1 deacetylates polyadenylate-binding protein 1 (PABP1), thereby suppressing nuclear export of polyadenylated mRNAs and translation to preserve energy under stress.

    更新日期:2017-08-23
  • Adult stem cells: Fat cells promote blood regeneration
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-26
    Kim Baumann

    Following irradiation, adipocytes derived from a specified subset of leptin receptor-positive cells in the bone marrow become a major source of stem cell factor for haematopoietic regeneration.

    更新日期:2017-08-23
  • Genome organization: A vision of 3D chromatin organization
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-23
    Kim Baumann

    A new imaging technique (ChromEMT) enables the visualization of the local polymer structure and global 3D organization of chromatin in the nucleus of intact interphase and mitotic human cells.

    更新日期:2017-08-23
  • Cancer biology: A Neat target of p53
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-02
    Eytan Zlotorynski

    The lincRNA Neat1 is a p53 target gene that can suppress the initiation of pancreatic cancer.

    更新日期:2017-08-23
  • Genes and molecular pathways underpinning ciliopathies
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-12
    Jeremy F. Reiter, Michel R. Leroux

    Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped us to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling. Both basic biological and clinical studies are uncovering novel ciliopathies and the ciliary proteins involved. The assignment of these proteins to different ciliary structures, processes and ciliopathy subclasses (first order and second order) provides insights into how this versatile organelle is built, compartmentalized and functions in diverse ways that are essential for human health.

    更新日期:2017-08-23
  • Understanding nucleosome dynamics and their links to gene expression and DNA replication
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-05-24
    William K. M. Lai, B. Franklin Pugh

    Advances in genomics technology have provided the means to probe myriad chromatin interactions at unprecedented spatial and temporal resolution. This has led to a profound understanding of nucleosome organization within the genome, revealing that nucleosomes are highly dynamic. Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general regulatory factors, chromatin remodellers, chaperones and polymerases. It is now known that these dynamics regulate diverse cellular processes ranging from gene transcription to DNA replication and repair.

    更新日期:2017-08-23
  • Mechanisms of DNA–protein crosslink repair
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-06-28
    Julian Stingele, Roberto Bellelli, Simon J. Boulton

    Covalent DNA–protein crosslinks (DPCs, also known as protein adducts) of topoisomerases and other proteins with DNA are highly toxic DNA lesions. Of note, chemical agents that induce DPCs include widely used classes of chemotherapeutics. Their bulkiness blocks virtually every chromatin-based process and makes them intractable for repair by canonical repair pathways. Distinct DPC repair pathways employ unique points of attack and are crucial for the maintenance of genome stability. Tyrosyl-DNA phosphodiesterases (TDPs) directly hydrolyse the covalent linkage between protein and DNA. The MRE11–RAD50–NBS1 (MRN) nuclease complex targets the DNA component of DPCs, excising the fragment affected by the lesion, whereas proteases of the spartan (SPRTN)/weak suppressor of SMT3 protein 1 (Wss1) family target the protein component. Loss of these pathways renders cells sensitive to DPC-inducing chemotherapeutics, and DPC repair pathways are thus attractive targets for combination cancer therapy.

    更新日期:2017-08-23
  • Classification and function of small open reading frames
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-12
    Juan-Pablo Couso, Pedro Patraquim

    Small open reading frames (smORFs) of 100 codons or fewer are usually — if arbitrarily — excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila

    更新日期:2017-08-23
  • Splicing: Phasing alternative exons
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-26
    Eytan Zlotorynski

    Two papers report a new mechanism of controlling alternative splicing through phase separation-mediated formation of higher-order assemblies of splicing factors.

    更新日期:2017-08-18
  • Cancer biology: A Neat target of p53
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-02
    Eytan Zlotorynski

    The lincRNA Neat1 is a p53 target gene that can suppress the initiation of pancreatic cancer.

    更新日期:2017-08-18
  • Adult stem cells: Fat cells promote blood regeneration
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-26
    Kim Baumann

    Following irradiation, adipocytes derived from a specified subset of leptin receptor-positive cells in the bone marrow become a major source of stem cell factor for haematopoietic regeneration.

    更新日期:2017-08-18
  • Stress responses: SIRT1 puts an embargo on mRNA export
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Paulina Strzyz

    Sirtuin 1 deacetylates polyadenylate-binding protein 1 (PABP1), thereby suppressing nuclear export of polyadenylated mRNAs and translation to preserve energy under stress.

    更新日期:2017-08-18
  • Epigenetics: Getting instructions from mum
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-02
    Paulina Strzyz

    Patterns of histone H3 Lys27 trimethylation are maternally inherited in both fly and mammalian embryos, and control gene expression during early development.

    更新日期:2017-08-18
  • Understanding nucleosome dynamics and their links to gene expression and DNA replication
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-05-24
    William K. M. Lai, B. Franklin Pugh

    Advances in genomics technology have provided the means to probe myriad chromatin interactions at unprecedented spatial and temporal resolution. This has led to a profound understanding of nucleosome organization within the genome, revealing that nucleosomes are highly dynamic. Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general regulatory factors, chromatin remodellers, chaperones and polymerases. It is now known that these dynamics regulate diverse cellular processes ranging from gene transcription to DNA replication and repair.

    更新日期:2017-08-18
  • Mechanisms of DNA–protein crosslink repair
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-06-28
    Julian Stingele, Roberto Bellelli, Simon J. Boulton

    Covalent DNA–protein crosslinks (DPCs, also known as protein adducts) of topoisomerases and other proteins with DNA are highly toxic DNA lesions. Of note, chemical agents that induce DPCs include widely used classes of chemotherapeutics. Their bulkiness blocks virtually every chromatin-based process and makes them intractable for repair by canonical repair pathways. Distinct DPC repair pathways employ unique points of attack and are crucial for the maintenance of genome stability. Tyrosyl-DNA phosphodiesterases (TDPs) directly hydrolyse the covalent linkage between protein and DNA. The MRE11–RAD50–NBS1 (MRN) nuclease complex targets the DNA component of DPCs, excising the fragment affected by the lesion, whereas proteases of the spartan (SPRTN)/weak suppressor of SMT3 protein 1 (Wss1) family target the protein component. Loss of these pathways renders cells sensitive to DPC-inducing chemotherapeutics, and DPC repair pathways are thus attractive targets for combination cancer therapy.

    更新日期:2017-08-18
  • Genes and molecular pathways underpinning ciliopathies
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-12
    Jeremy F. Reiter, Michel R. Leroux

    Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped us to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling. Both basic biological and clinical studies are uncovering novel ciliopathies and the ciliary proteins involved. The assignment of these proteins to different ciliary structures, processes and ciliopathy subclasses (first order and second order) provides insights into how this versatile organelle is built, compartmentalized and functions in diverse ways that are essential for human health.

    更新日期:2017-08-18
  • Classification and function of small open reading frames
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-12
    Juan-Pablo Couso, Pedro Patraquim

    A comprehensive analysis of small open reading frames (smORFs) in flies, mice and humans supports their classification into different functional groups, from inert DNA sequences to transcribed and translated smORFs that have various activities. The different smORF classes could represent steps in gene, peptide and protein evolution.

    更新日期:2017-08-18
  • Chromosome biology: Structuring interphase chromatin
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-06-28
    Eytan Zlotorynski

    The oligomerization of scaffold attachment factor A through its binding to chromatin-associated RNAs regulates the structure of interphase chromosomes.

    更新日期:2017-08-18
  • Stem cells: Colonic organoids for drug testing and colorectal disease modelling
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-05
    Kim Baumann

    Two studies report the generation of human colonic organoids, which could be useful for disease modelling and drug testing.

    更新日期:2017-08-18
  • Ribosome cycle emerges from DNA replication
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-06-14
    Raymond Kaempfer

    A modification of Meselson and Stahl's density gradient centrifugation method and a rare Texan yeast helped show that eukaryotic ribosomes dissociate and reform during translation.

    更新日期:2017-08-18
  • Cancer biology: Therapy-induced transcription is cryptically widespread
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-06-28
    Darren J. Burgess

    Inhibitors of DNA methyltransferases and of histone deacetylases induce transcription from cryptic transposable elements, which results in 5′-truncated and mis-spliced proteins that may increase cancer immunogenicity.

    更新日期:2017-08-18
  • Circadian rhythms: Replication keeps the clock ticking
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-05
    Paulina Strzyz

    DNA replication regulates nucleosome dynamics at the promoter of a negative element of the circadian clock, thereby providing regulatory feedback into circadian rhythms.

    更新日期:2017-08-18
  • Physiological functions of programmed DNA breaks in signal-induced transcription
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-05-24
    Janusz Puc, Aneel K. Aggarwal, Michael G. Rosenfeld

    The idea that signal-dependent transcription might involve the generation of transient DNA nicks or even breaks in the regulatory regions of genes, accompanied by activation of DNA damage repair pathways, would seem to be counterintuitive, as DNA damage is usually considered harmful to cellular integrity.

    更新日期:2017-08-18
  • Unfolded protein response: Reacting to membrane stress
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-21
    Paulina Strzyz

    Changes in endoplasmic reticulum membrane composition induce the oligomerization of Ire1 and activate the unfolded protein response.

    更新日期:2017-08-18
  • Vascular heterogeneity and specialization in development and disease
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-05-24
    Michael Potente, Taija Mäkinen

    Blood and lymphatic vessels pervade almost all body tissues and have numerous essential roles in physiology and disease. The inner lining of these networks is formed by a single layer of endothelial cells, which is specialized according to the needs of the tissue that it supplies. Whereas the general mechanisms of blood and lymphatic vessel development are being defined with increasing molecular precision, studies of the processes of endothelial specialization remain mostly descriptive. Recent insights from genetic animal models illuminate how endothelial cells interact with each other and with their tissue environment, providing paradigms for vessel type- and organ-specific endothelial differentiation. Delineating these governing principles will be crucial for understanding how tissues develop and maintain, and how their function becomes abnormal in disease.

    更新日期:2017-08-18
  • Non-homologous DNA end joining and alternative pathways to double-strand break repair
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-05-17
    Howard H. Y. Chang, Nicholas R. Pannunzio, Noritaka Adachi, Michael R. Lieber

    DNA double-strand breaks (DSBs) are the most dangerous type of DNA damage because they can result in the loss of large chromosomal regions. In all mammalian cells, DSBs that occur throughout the cell cycle are repaired predominantly by the non-homologous DNA end joining (NHEJ) pathway. Defects in NHEJ result in sensitivity to ionizing radiation and the ablation of lymphocytes. The NHEJ pathway utilizes proteins that recognize, resect, polymerize and ligate the DNA ends in a flexible manner. This flexibility permits NHEJ to function on a wide range of DNA-end configurations, with the resulting repaired DNA junctions often containing mutations. In this Review, we discuss the most recent findings regarding the relative involvement of the different NHEJ proteins in the repair of various DNA-end configurations. We also discuss the shunting of DNA-end repair to the auxiliary pathways of alternative end joining (a-EJ) or single-strand annealing (SSA) and the relevance of these different pathways to human disease.

    更新日期:2017-08-18
  • Mechanisms of DNA replication termination
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-05-24
    James M. Dewar, Johannes C. Walter

    Genome duplication is carried out by pairs of replication forks that assemble at origins of replication and then move in opposite directions. DNA replication ends when converging replication forks meet. During this process, which is known as replication termination, DNA synthesis is completed, the replication machinery is disassembled and daughter molecules are resolved. In this Review, we outline the steps that are likely to be common to replication termination in most organisms, namely, fork convergence, synthesis completion, replisome disassembly and decatenation. We briefly review the mechanism of termination in the bacterium Escherichia coli and in simian virus 40 (SV40) and also focus on recent advances in eukaryotic replication termination. In particular, we discuss the recently discovered E3 ubiquitin ligases that control replisome disassembly in yeast and higher eukaryotes, and how their activity is regulated to avoid genome instability.

    更新日期:2017-08-18
  • Transcriptional and epigenetic control of brown and beige adipose cell fate and function
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-12
    Takeshi Inagaki, Juro Sakai, Shingo Kajimura

    Nature Reviews Molecular Cell Biology17, 480–495 (2016)Two errors in Table 1 of the HTML and PDF versions of this article have been corrected. In addition, corrections to a number of protein definitions have been made.

    更新日期:2017-08-18
  • The winding path of protein methylation research: milestones and new frontiers
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-05-17
    Jernej Murn, Yang Shi

    In 1959, while analysing the bacterial flagellar proteins, Ambler and Rees observed an unknown species of amino acid that they eventually identified as methylated lysine. Over half a century later, protein methylation is known to have a regulatory role in many essential cellular processes that

    更新日期:2017-08-18
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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