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SMC-5/6 complex subunit NSE-1 plays a crucial role in meiosis and DNA repair in Caenorhabditis elegans DNA Repair (IF 3.8) Pub Date : 2024-03-12 Arome Solomon Odiba, Chiemekam Samuel Ezechukwu, Guiyan Liao, Ye Hong, Wenxia Fang, Cheng Jin, Anton Gartner, Bin Wang
The Smc5/6 complex is evolutionarily conserved across all eukaryotes and plays a pivotal role in preserving genomic stability. Mutations in genes encoding Smc5/6 complex subunits have been associated with human lung disease, immunodeficiency, and chromosome breakage syndrome. Despite its critical importance, much about the Smc5/6 complex remains to be elucidated. Various evidences have suggested possible
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Mitochondrial transcription factor A (TFAM) has 5′-deoxyribose phosphate lyase activity in vitro DNA Repair (IF 3.8) Pub Date : 2024-03-08 Wenxin Zhao, Adil S. Hussen, Bret D. Freudenthal, Zucai Suo, Linlin Zhao
Mitochondrial DNA (mtDNA) plays a key role in mitochondrial and cellular functions. mtDNA is maintained by active DNA turnover and base excision repair (BER). In BER, one of the toxic repair intermediates is 5′-deoxyribose phosphate (5′dRp). Human mitochondrial DNA polymerase γ has weak dRp lyase activities, and another known dRp lyase in the nucleus, human DNA polymerase β, can also localize to mitochondria
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What are the DNA lesions underlying formaldehyde toxicity? DNA Repair (IF 3.8) Pub Date : 2024-03-07 Bente Benedict, Stella Munkholm Kristensen, Julien P. Duxin
Formaldehyde is a highly reactive organic compound. Humans can be exposed to exogenous sources of formaldehyde, but formaldehyde is also produced endogenously as a byproduct of cellular metabolism. Because formaldehyde can react with DNA, it is considered a major endogenous source of DNA damage. However, the nature of the lesions underlying formaldehyde toxicity in cells remains vastly unknown. Here
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Comparing Mfd- and UvrD-dependent models of transcription coupled DNA repair in live Escherichia coli using single-molecule tracking DNA Repair (IF 3.8) Pub Date : 2024-03-07 Elżbieta Kaja, Donata Vijande, Justyna Kowalczyk, Micha Michalak, Jacek Gapiński, Carolin Kobras, Philippa Rolfe, Mathew Stracy
During transcription-coupled DNA repair (TCR) the detection of DNA damage and initiation of nucleotide excision repair (NER) is performed by translocating RNA polymerases (RNAP), which are arrested upon encountering bulky DNA lesions. Two opposing models of the subsequent steps of TCR in bacteria exist. In the first model, stalled RNAPs are removed from the damage site by recruitment of Mfd which dislodges
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Deletions initiated by the vaccinia virus TopIB protein in yeast DNA Repair (IF 3.8) Pub Date : 2024-03-06 Jang Eun Cho, Samantha Shaltz, Lyudmila Yakovleva, Stewart Shuman, Sue Jinks-Robertson
The type IB topoisomerase of budding yeast (yTop1) generates small deletions in tandem repeats through a sequential cleavage mechanism and larger deletions with random endpoints through the nonhomologous end-joining (NHEJ) pathway. Vaccinia virus Top1 (vTop1) is a minimized version of the eukaryal TopIB enzymes and uniquely has a strong consensus cleavage sequence: the pentanucleotide (T/C)CCTTp↓.
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Dominant roles of BRCA1 in cellular tolerance to a chain-terminating nucleoside analog, alovudine DNA Repair (IF 3.8) Pub Date : 2024-03-05 Md Bayejid Hosen, Ryotaro Kawasumi, Kouji Hirota
Alovudine is a chain-terminating nucleoside analog (CTNA) that is frequently used as an antiviral and anticancer agent. Generally, CTNAs inhibit DNA replication after their incorporation into nascent DNA during DNA synthesis by suppressing subsequent polymerization, which restricts the proliferation of viruses and cancer cells. Alovudine is a thymidine analog used as an antiviral drug. However, the
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DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity DNA Repair (IF 3.8) Pub Date : 2024-02-29 Amir Hozhabrpour, Marzieh Mojbafan, Fahimeh Palizban, Fatemeh vahidnezhad, Saeed Talebi, Maliheh Amani, Masoud Garshasbi, Anoosh Naghavi, Raziyeh Khalesi, Parvin Mansouri, Soheila Sotoudeh, Hamidreza Mahmoudi, Aida Varghaei, Maryam Daneshpazhooh, Fatemeh Karimi, Sirous Zeinali, Elnaz Kalamati, Jouni Uitto, Leila Youssefian, Hassan Vahidnezhad
Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome
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Identification of ATM-dependent long non-coding RNAs induced in response to DNA damage DNA Repair (IF 3.8) Pub Date : 2024-02-15 Marta Podralska, Marcin Piotr Sajek, Antonina Bielicka, Magdalena Żurawek, Iwona Ziółkowska-Suchanek, Katarzyna Iżykowska, Tomasz Kolenda, Marta Kazimierska, Marta Elżbieta Kasprzyk, Weronika Sura, Barbara Pietrucha, Bożena Cukrowska, Natalia Rozwadowska, Agnieszka Dzikiewicz- Krawczyk
DNA damage response (DDR) is a complex process, essential for cell survival. Especially deleterious type of DNA damage are DNA double-strand breaks (DSB), which can lead to genomic instability and malignant transformation if not repaired correctly. The central player in DSB detection and repair is the ATM kinase which orchestrates the action of several downstream factors. Recent studies have suggested
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A-T neurodegeneration and DNA damage-induced transcriptional stress DNA Repair (IF 3.8) Pub Date : 2024-02-15 Tanya T. Paull, Phillip R. Woolley
Loss of the ATM protein kinase in humans results in Ataxia-telangiectasia, a disorder characterized by childhood-onset neurodegeneration of the cerebellum as well as cancer predisposition and immunodeficiency. Although many aspects of ATM function are well-understood, the mechanistic basis of the progressive cerebellar ataxia that occurs in patients is not. Here we review recent progress related to
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RNF4 prevents genomic instability caused by chronic DNA under-replication DNA Repair (IF 3.8) Pub Date : 2024-02-07 Marissa K. Oram, Ryan M. Baxley, Emily M. Simon, Kevin Lin, Ya-Chu Chang, Liangjun Wang, Chad L. Myers, Anja-Katrin Bielinsky
Eukaryotic genome stability is maintained by a complex and diverse set of molecular processes. One class of enzymes that promotes proper DNA repair, replication and cell cycle progression comprises small ubiquitin-like modifier (SUMO)-targeted E3 ligases, or STUbLs. Previously, we reported a role for the budding yeast STUbL synthetically lethal with (Slx) 5/8 in preventing G/M-phase arrest in a minichromosome
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DNA polymerase λ Loop1 variant yields unexpected gain-of-function capabilities in nonhomologous end-joining DNA Repair (IF 3.8) Pub Date : 2024-02-03 Andrea M. Kaminski, Kishore K. Chiruvella, Dale A. Ramsden, Katarzyna Bebenek, Thomas A. Kunkel, Lars C. Pedersen
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Variants in the first methionine of RAD51C are homologous recombination proficient due to an alternative start site DNA Repair (IF 3.8) Pub Date : 2024-02-01 Hayley L. Rein, Kara A. Bernstein
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Microglial inflammation in genome instability: A neurodegenerative perspective DNA Repair (IF 3.8) Pub Date : 2024-01-24 Nina L. Maliar, Emily J. Talbot, Abigail R. Edwards, Svetlana V. Khoronenkova
The maintenance of genome stability is crucial for cell homeostasis and tissue integrity. Numerous human neuropathologies display chronic inflammation in the central nervous system, set against a backdrop of genome instability, implying a close interplay between the DNA damage and immune responses in the context of neurological disease. Dissecting the molecular mechanisms of this crosstalk is essential
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Loss of alkyladenine DNA glycosylase alters gene expression in the developing mouse brain and leads to reduced anxiety and improved memory DNA Repair (IF 3.8) Pub Date : 2024-01-22 Diana L. Bordin, Kayla Grooms, Nicola P. Montaldo, Sarah L. Fordyce Martin, Pål Sætrom, Leona D. Samson, Magnar Bjørås, Barbara van Loon
Neurodevelopment is a tightly coordinated process, during which the genome is exposed to spectra of endogenous agents at different stages of differentiation. Emerging evidence indicates that DNA damage is an important feature of developing brain, tightly linked to gene expression and neuronal activity. Some of the most frequent DNA damage includes changes to DNA bases, which are recognized by DNA glycosylases
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Single-molecule analysis of purified proteins and nuclear extracts: Insights from 8-oxoguanine glycosylase 1 DNA Repair (IF 3.8) Pub Date : 2024-01-17 Matthew A. Schaich, Tyler M. Weaver, Vera Roginskaya, Bret D. Freudenthal, Bennett Van Houten
By observing one molecule at a time, single-molecule studies can offer detailed insights about biomolecular processes including on rates, off rates, and diffusivity of molecules on strands of DNA. A recent technological advance (Single-molecule Analysis of DNA-binding proteins from Nuclear Extracts, SMADNE) has lowered the barrier to entry for single-molecule studies, and single-molecule dynamics can
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Super-resolution GSDIM microscopy unveils distinct nanoscale characteristics of DNA repair foci under diverse genotoxic stress DNA Repair (IF 3.8) Pub Date : 2024-01-16 Haibin Qian, Audrey Margaretha Plat, Ard Jonker, Ron A. Hoebe, Przemek Krawczyk
DNA double-strand breaks initiate the DNA damage response (DDR), leading to the accumulation of repair proteins at break sites and the formation of the-so-called foci. Various microscopy methods, such as wide-field, confocal, electron, and super-resolution microscopy, have been used to study these structures. However, the impact of different DNA-damaging agents on their (nano)structure remains unclear
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Corrigendum to “Over-expression of miR-100 is responsible for the low-expression of ATM in the human glioma cell line: M059J” [DNA Repair 9 (2010) 1170-1175] DNA Repair (IF 3.8) Pub Date : 2024-01-13 Wooi Loon Ng, Dan Yan, Xiangming Zhang, Yin-Yuan Mo, Ya Wang
Abstract not available
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Chromosomal single-strand break repair and neurological disease: Implications on transcription and emerging genomic tools DNA Repair (IF 3.8) Pub Date : 2024-01-11 Arwa A. Abugable, Sarah Antar, Sherif F. El-Khamisy
Cells are constantly exposed to various sources of DNA damage that pose a threat to their genomic integrity. One of the most common types of DNA breaks are single-strand breaks (SSBs). Mutations in the repair proteins that are important for repairing SSBs have been reported in several neurological disorders. While several tools have been utilised to investigate SSBs in cells, it was only through recent
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Catalytic activity of OGG1 is impaired by Zinc deficiency DNA Repair (IF 3.8) Pub Date : 2024-01-10 Priyanka Sharma, Carmen P. Wong, Emily Ho, Harini Sampath
Oxidative stress-induced DNA base modifications, if unrepaired, can increase mutagenesis and genomic instability, ultimately leading to cell death. Cells predominantly use the base excision repair (BER) pathway to repair oxidatively-induced non-helix distorting lesions. BER is initiated by DNA glycosylases, such as 8-oxoguanine DNA glycosylase (OGG1), which repairs oxidatively modified guanine bases
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Ku80 is indispensable for repairing DNA double-strand breaks at highly methylated sites in human HCT116 cells DNA Repair (IF 3.8) Pub Date : 2024-01-07 Mengtan Xing, Yanhong Xiong, Yong Zhang
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DONSON: Slding in 2 the limelight DNA Repair (IF 3.8) Pub Date : 2023-12-23 G, r, a, n, t, , S, ., , S, t, e, w, a, r, t
For over a decade, it has been known that yeast Sld2, Dpb11, GINS and Polε form the pre-loading complex (pre-LC), which is recruited to a CDC45-bound MCM2–7 complex by the Sld3/Sld7 heterodimer in a phospho-dependent manner. Whilst functional orthologs of Dbp11 (TOPBP1), Sld3 (TICRR) and Sld7 (MTBP) have been identified in metazoans, controversy has surrounded the identity of the Sld2 ortholog. It
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Biochemical analysis of H2O2-induced mutation spectra revealed that multiple damages were involved in the mutational process DNA Repair (IF 3.8) Pub Date : 2023-12-22 Tomohiko Sugiyama, Mahima R. Sanyal
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Contents of previous 3 special issues in this series of perspectives DNA Repair (IF 3.8) Pub Date : 2023-12-20 P, e, n, n, y, , J, e, g, g, o
Abstract not available
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Cutting Edge Perspectives in genome maintenance X DNA Repair (IF 3.8) Pub Date : 2023-12-20 P, e, n, n, y, , A, n, n, , J, e, g, g, o
Abstract not available
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Real-time single-molecule visualization using DNA curtains reveals the molecular mechanisms underlying DNA repair pathways DNA Repair (IF 3.8) Pub Date : 2023-12-14 Subin Kim, Youngseo Kim, Ja Yil Lee
The demand for direct observation of biomolecular interactions provides new insights into the molecular mechanisms underlying many biological processes. Single-molecule imaging techniques enable real-time visualization of individual biomolecules, providing direct observations of protein machines. Various single-molecule imaging techniques have been developed and have contributed to breakthroughs in
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Positive and negative regulators of RAD51/DMC1 in homologous recombination and DNA replication DNA Repair (IF 3.8) Pub Date : 2023-12-13 Masaru Ito, Yurika Fujita, Akira Shinohara
RAD51 recombinase plays a central role in homologous recombination (HR) by forming a nucleoprotein filament on single-stranded DNA (ssDNA) to catalyze homology search and strand exchange between the ssDNA and a homologous double-stranded DNA (dsDNA). The catalytic activity of RAD51 assembled on ssDNA is critical for the DNA-homology-mediated repair of DNA double-strand breaks in somatic and meiotic
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FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe DNA Repair (IF 3.8) Pub Date : 2023-12-05 Lucy Jennings, Heather Andrews Walters, Tyler J. McCraw, Joshua L. Turner, Jennifer M. Mason
WEE1 kinase phosphorylates CDK1 and CDK2 to regulate origin firing and mitotic entry. Inhibition of WEE1 has become an attractive target for cancer therapy due to the simultaneous induction of replication stress and inhibition of the G2/M checkpoint. WEE1 inhibition in cancer cells with high levels of replication stress results in induction of replication catastrophe and mitotic catastrophe. To increase
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Targeted nuclear irradiation with a proton microbeam induces oxidative DNA base damage and triggers the recruitment of DNA glycosylases OGG1 and NTH1 DNA Repair (IF 3.8) Pub Date : 2023-12-05 Elena Robeska, Kévin Lalanne, François Vianna, Haser Hasan Sutcu, Andriy Khobta, Didier Busso, J. Pablo Radicella, Anna Campalans, Céline Baldeyron
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Potential cGAS-STING pathway functions in DNA damage responses, DNA replication and DNA repair DNA Repair (IF 3.8) Pub Date : 2023-11-30 Christian Zierhut
The major innate immune responder to the DNA of pathogens is the cyclic GMP-AMP (cGAMP) synthase (cGAS) - stimulator of interferon genes (STING) pathway. Most prominently, the outcome of cGAS signalling is the activation of inflammatory transcription through interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB). In addition, the cGAS-STING pathway can lead to the direct modulation
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Defects in DNA damage responses in SWI/SNF mutant cells and their impact on immune responses DNA Repair (IF 3.8) Pub Date : 2023-11-28 Katheryn A.G. Begg, Hanna Braun, Nagham Ghaddar, Lillian Wu, Jessica A. Downs
The mammalian SWI/SNF chromatin remodelling complexes are commonly dysregulated in cancer. These complexes contribute to maintaining genome stability through a variety of pathways. Recent research has highlighted an important interplay between genome instability and immune signalling, and evidence suggests that this interplay can modulate the response to immunotherapy. Here, we review emerging studies
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Somatic mutation patterns at Ig and Non-Ig Loci DNA Repair (IF 3.8) Pub Date : 2023-11-28 Edward J. Steele, Andrew Franklin, Robyn A. Lindley
The reverse transcriptase (RT) model of immunoglobulin (Ig) somatic hypermutation (SHM) has received insufficient scientific attention. This is understandable given that DNA deamination mediated by activation-induced deaminase (AID), the initiating step of Ig SHM, has dominated experiments since 2002. We summarise some key history of the RT Ig SHM model dating to 1987. For example, it is now established
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A non-canonical nucleotide from viral genomes interferes with the oxidative DNA damage repair system DNA Repair (IF 3.8) Pub Date : 2023-11-20 Anna V. Yudkina, Anton V. Endutkin, Evgeniia A. Diatlova, Dmitry O. Zharkov
Oxidative damage is a major source of genomic instability in all organisms with the aerobic metabolism. 8-Oxoguanine (8-oxoG), an abundant oxidized purine, is mutagenic and must be controlled by a dedicated DNA repair system (GO system) that prevents G:C→T:A transversions through an easily formed 8-oxoG:A mispair. In some forms, the GO system is present in nearly all cellular organisms. However, recent
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Interaction of mitoxantrone with abasic sites - DNA strand cleavage and inhibition of apurinic/apyrimidinic endonuclease 1, APE1 DNA Repair (IF 3.8) Pub Date : 2023-11-20 Irina G. Minko, Samantha A. Moellmer, Michael M. Luzadder, Rachana Tomar, Michael P. Stone, Amanda K. McCullough, R. Stephen Lloyd
Mitoxantrone (1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]-anthracene-9,10-dione) is a clinically-relevant synthetic anthracenedione that functions as a topoisomerase II poison by trapping DNA double-strand break intermediates. Mitoxantrone binds to DNA via both stacking interactions with DNA bases and hydrogen bonding with the sugar-phosphate backbone. It has been shown that mitoxantrone
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The impact of chromatin on double-strand break repair: Imaging tools and discoveries DNA Repair (IF 3.8) Pub Date : 2023-11-16 Marit A.E. van Bueren, Aniek Janssen
Eukaryotic nuclei are constantly being exposed to factors that break or chemically modify the DNA. Accurate repair of this DNA damage is crucial to prevent DNA mutations and maintain optimal cell function. To overcome the detrimental effects of DNA damage, a multitude of repair pathways has evolved. These pathways need to function properly within the different chromatin domains present in the nucleus
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NEIL3 promotes cell proliferation of ccRCC via the cyclin D1-Rb-E2F1 feedback loop regulation DNA Repair (IF 3.8) Pub Date : 2023-11-19 Mengzhao Zhang, Yunzhong Jiang, Jichang Wang, Yangyang Yue, Wei Liu, Lu Wang, Yan Li, Weiyi Wang, Hui Cai, Zezhong Yang, Minghai Ma, Shaoying Lu, Jinhai Fan
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FAM21 interacts with Ku to promote the localization of WASH to DNA double strand break sites DNA Repair (IF 3.8) Pub Date : 2023-11-18 Tao Wang, Ai-Xue Zheng, Ping Li, Tuo Tang, Lu-Ping Zhang, Yu Hong, Xian Hong, Zhi-Hui Deng
Cytoplasmic FAM21 works as a guiding protein in Wiskott–Aldrich Syndrome Protein and SCAR Homolog (WASH) complex by linking WASH complex to endosomes through its interaction with retromer. Recently, we have reported that nuclear WASH localizes to DNA double strand break (DSB) sites to promote DNA repair through non-homologous end-joining (NHEJ). However, whether FAM21, the close partner of WASH, is
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The entanglement of DNA damage and pattern recognition receptor signaling DNA Repair (IF 3.8) Pub Date : 2023-11-15 Cindy T. Ha, Maha M. Tageldein, Shane M. Harding
Cells are under constant pressure to suppress DNA damage originating from both exogenous and endogenous sources. Cellular responses to DNA damage help to prevent mutagenesis and cell death that arises when DNA damage is either left unrepaired or repaired inaccurately. During the “acute phase” of DNA damage signaling, lesions are recognized, processed, and repaired to restore the primary DNA sequence
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Regulatory apoptotic fragment of PARP1 complements catalytic fragment for PAR and DNA-dependent activity but inhibits DNA-induced catalytic stimulation of PARP2 DNA Repair (IF 3.8) Pub Date : 2023-11-15 Waghela Deeksha, Eerappa Rajakumara
To maintain tissue homeostasis, cell proliferation is balanced by cell death. PARP1 is an important protein involved in both processes. Upon sensing DNA damage, PARP1 forms poly(ADP-ribose) (PAR) chains to recruit the repair proteins, ensuring genome integrity and faithful cell proliferation. In addition, PAR also regulates the activity of PARP1. Persistent DNA damage can signal the cell to progress
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DNA repair deficiency and the immune microenvironment: A pathways perspective DNA Repair (IF 3.8) Pub Date : 2023-11-13 Yuzhen Zhou, Kent W. Mouw
Timely and accurate repair of DNA damage is required for genomic stability, but DNA repair pathways are often lost or altered in tumors. In addition to directly impacting tumor cell response to DNA damage, DNA repair deficiency can also alter the immune microenvironment via changes in innate and adaptive immune signaling. In some settings, these changes can lead to increased sensitivity to immune checkpoint
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Telomeres as hotspots for innate immunity and inflammation DNA Repair (IF 3.8) Pub Date : 2023-11-05 Joe Nassour, Sara Przetocka, Jan Karlseder
Aging is marked by the gradual accumulation of deleterious changes that disrupt organ function, creating an altered physiological state that is permissive for the onset of prevalent human diseases. While the exact mechanisms governing aging remain a subject of ongoing research, there are several cellular and molecular hallmarks that contribute to this biological process. This review focuses on two
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Regulation of DNA damage-induced HLA Class I Presentation DNA Repair (IF 3.8) Pub Date : 2023-11-01 Yuki Uchihara, Atsushi Shibata
Immune checkpoint inhibitors (ICI) are cancer therapies that restore anti-tumor immunity; however, only a small percentage of patients have been completely cured by ICI alone. Multiple approaches in combination with other modalities have been used to improve the efficacy of ICI therapy. Among conventional cancer treatments, radiotherapy or DNA damage-based chemotherapy is a promising candidate as a
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Targeting mitotic regulators in cancer as a strategy to enhance immune recognition DNA Repair (IF 3.8) Pub Date : 2023-10-18 Mateusz Gregorczyk, Eileen E. Parkes
Eukaryotic DNA has evolved to be enclosed within the nucleus to protect the cellular genome from autoinflammatory responses driven by the immunogenic nature of cytoplasmic DNA. Cyclic GMP-AMP Synthase (cGAS) is the cytoplasmic dsDNA sensor, which upon activation of Stimulator of Interferon Genes (STING), mediates production of pro-inflammatory interferons (IFNs) and interferon stimulated genes (ISGs)
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UvrD-like helicase Hmi1 Has an ATP independent role in yeast mitochondrial DNA maintenance DNA Repair (IF 3.8) Pub Date : 2023-10-11 Sirelin Sillamaa, Vlad–Julian Piljukov, Iris Vaask, Tiina Sedman, Priit Jõers, Juhan Sedman
Hmi1 is a UvrD-like DNA helicase required for the maintenance of the yeast Saccharomyces cerevisiae mitochondrial DNA (mtDNA). Deletion of the HMI1 ORF leads to the formation of respiration-deficient petite mutants, which either contain a short fragment of mtDNA arranged in tandem repeats or lack mtDNA completely. Here we characterize point mutants of the helicase designed to target the ATPase or ssDNA
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‘From R-lupus to cancer’: Reviewing the role of R-loops in innate immune responses DNA Repair (IF 3.8) Pub Date : 2023-10-06 Leanne Bradley, Kienan I. Savage
Cells possess an inherent and evolutionarily conserved ability to detect and respond to the presence of foreign and pathological ‘self’ nucleic acids. The result is the stimulation of innate immune responses, signalling to the host immune system that defence mechanisms are necessary to protect the organism. To date, there is a vast body of literature describing innate immune responses to various nucleic
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Presenilin-1, mutated in familial Alzheimer’s disease, maintains genome stability via a γ-secretase dependent way DNA Repair (IF 3.8) Pub Date : 2023-09-30 Xihan Guo, Minyan Jiang, Xueqin Dai, Jie Shen, Xu Wang
Mutations in Presenilin-1 (PS1) account for over 80 % mutations linked to familial Alzheimer’s disease (AD). However, the mechanisms of action of PS1 mutations in causing familial AD are not fully understood, limiting opportunities to develop targeted disease-modifying therapies for individuals carrying PS1 mutation. To gain more comprehensive insights into the impact of PS1 mutations on genome stability
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Multi-scale cellular imaging of DNA double strand break repair DNA Repair (IF 3.8) Pub Date : 2023-09-19 Tim Heemskerk, Gerarda van de Kamp, Jeroen Essers, Roland Kanaar, Maarten W. Paul
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Alteration in the chromatin landscape during the DNA damage response: Continuous rotation of the gear driving cellular senescence and aging DNA Repair (IF 3.8) Pub Date : 2023-09-17 Jianghao Qian, Xiangyu Zhou, Kozo Tanaka, Akiko Takahashi
The DNA damage response (DDR) is a crucial biological mechanism for maintaining cellular homeostasis in living organisms. This complex process involves a cascade of signaling pathways that orchestrate the sensing and processing of DNA lesions. Perturbations in this process may cause DNA repair failure, genomic instability, and irreversible cell cycle arrest, known as cellular senescence, potentially
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Chromatin meets the cytoskeleton: the importance of nuclear actin dynamics and associated motors for genome stability DNA Repair (IF 3.8) Pub Date : 2023-09-16 Hans-Peter Wollscheid, Helle D. Ulrich
The actin cytoskeleton is of fundamental importance for numerous cellular processes, including intracellular transport, cell plasticity, and cell migration. However, functions of filamentous actin (F-actin) in the nucleus remain understudied due to the comparatively low abundance of nuclear actin and the resulting experimental limitations to its visualization. Owing to recent technological advances
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Live cell transcription-coupled nucleotide excision repair dynamics revisited DNA Repair (IF 3.8) Pub Date : 2023-09-09 Diana A. Llerena Schiffmacher, Katarzyna W. Kliza, Arjan F. Theil, Gert-Jan Kremers, Jeroen A.A. Demmers, Tomoo Ogi, Michiel Vermeulen, Wim Vermeulen, Alex Pines
Transcription–blocking lesions are specifically targeted by transcription-coupled nucleotide excision repair (TC-NER), which prevents DNA damage-induced cellular toxicity and maintains proper transcriptional processes. TC-NER is initiated by the stalling of RNA polymerase II (RNAPII), which triggers the assembly of TC-NER-specific proteins, namely CSB, CSA and UVSSA, which collectively control and
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How RNA impacts DNA repair DNA Repair (IF 3.8) Pub Date : 2023-09-09 Ning Tsao, Mohamed E. Ashour, Nima Mosammaparast
The central dogma of molecular biology posits that genetic information flows unidirectionally, from DNA, to RNA, and finally to protein. However, this directionality is broken in some cases, such as reverse transcription where RNA is converted to DNA by retroviruses and certain transposable elements. Our genomes have evolved and adapted to the presence of reverse transcription. Similarly, our genome
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Centromere: A Trojan horse for genome stability DNA Repair (IF 3.8) Pub Date : 2023-09-07 Andrea Scelfo, Daniele Fachinetti
Centromeres play a key role in the maintenance of genome stability to prevent carcinogenesis and diseases. They are specialized chromosome loci essential to ensure faithful transmission of genomic information across cell generations by mediating the interaction with spindle microtubules. Nonetheless, while fulfilling these essential roles, their distinct repetitive composition and susceptibility to
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TFIIH central activity in nucleotide excision repair to prevent disease DNA Repair (IF 3.8) Pub Date : 2023-09-07 Arjan F. Theil, David Häckes, Hannes Lans
The heterodecameric transcription factor IIH (TFIIH) functions in multiple cellular processes, foremost in nucleotide excision repair (NER) and transcription initiation by RNA polymerase II. TFIIH is essential for life and hereditary mutations in TFIIH cause the devastating human syndromes xeroderma pigmentosum, Cockayne syndrome or trichothiodystrophy, or combinations of these. In NER, TFIIH binds
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The C-terminal tail of Rad17, iVERGE, binds the 9‒1‒1 complex independently of AAA+ ATPase domains to provide another clamploader interface DNA Repair (IF 3.8) Pub Date : 2023-09-06 Yasunori Fukumoto, Tyuji Hoshino, Yuji Nakayama, Yasumitsu Ogra
The ATR pathway plays a crucial role in maintaining genome integrity as the major DNA damage checkpoint. It also attracts attention as a therapeutic target in cancer treatment. The Rad17–RFC2–5 complex loads the Rad9–Hus1–Rad1 (9–1–1) DNA clamp complex onto damaged chromatin to activate the ATR pathway. We previously reported that phosphorylation of a polyanionic C-terminal tail of human Rad17, iVERGE
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Metazoan nuclear pore complexes in gene regulation and genome stability DNA Repair (IF 3.8) Pub Date : 2023-09-04 Parisa Nobari, Valérie Doye, Charlene Boumendil
The nuclear pore complexes (NPCs), one of the hallmarks of eukaryotic nuclei, allow selective transport of macromolecules between the cytoplasm and the nucleus. Besides this canonical function, an increasing number of additional roles have been attributed to the NPCs and their constituents, the nucleoporins. Here we review recent insights into the mechanisms by which NPCs and nucleoporins affect transcription
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Finding significance: New perspectives in variant classification of the RAD51 regulators, BRCA2 and beyond DNA Repair (IF 3.8) Pub Date : 2023-08-19 Hayley L. Rein, Kara A. Bernstein
For many individuals harboring a variant of uncertain functional significance (VUS) in a homologous recombination (HR) gene, their risk of developing breast and ovarian cancer is unknown. Integral to the process of HR are BRCA1 and regulators of the central HR protein, RAD51, including BRCA2, PALB2, RAD51C and RAD51D. Due to advancements in sequencing technology and the continued expansion of cancer
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Holding it together: DNA end synapsis during non-homologous end joining DNA Repair (IF 3.8) Pub Date : 2023-08-08 Joseph J. Loparo
DNA double strand breaks (DSBs) are common lesions whose misrepair are drivers of oncogenic transformations. The non-homologous end joining (NHEJ) pathway repairs the majority of these breaks in vertebrates by directly ligating DNA ends back together. Upon formation of a DSB, a multiprotein complex is assembled on DNA ends which tethers them together within a synaptic complex. Synapsis is a critical
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Mechanistic insights from high resolution DNA damage analysis to understand mixed radiation exposure DNA Repair (IF 3.8) Pub Date : 2023-08-09 Pamela Akuwudike, Milagrosa López-Riego, Józef Ginter, Lei Cheng, Anna Wieczorek, Katarzyna Życieńska, Małgorzata Łysek-Gładysińska, Andrzej Wojcik, Beata Brzozowska, Lovisa Lundholm
Cells exposed to densely ionising high and scattered low linear energy transfer (LET) radiation (50 % dose of each) react more strongly than to the same dose of each separately. The relationship between DNA double strand break location inside the nucleus and chromatin structure was evaluated, using high-resolution transmission electron microscopy (TEM) in breast cancer MDA-MB-231 cells at 30 min post
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Spatio-temporal dynamics of the DNA glycosylase OGG1 in finding and processing 8-oxoguanine DNA Repair (IF 3.8) Pub Date : 2023-07-31 Luana Cintori, Anne-Marie Di Guilmi, Yvan Canitrot, Sebastien Huet, Anna Campalans
OGG1 is the DNA glycosylase responsible for the removal of the oxidative lesion 8-oxoguanine (8-oxoG) from DNA. The recognition of this lesion by OGG1 is a complex process that involves scanning the DNA for the presence of 8-oxoG, followed by recognition and lesion removal. Structural data have shown that OGG1 evolves through different stages of conformation onto the DNA, corresponding to elementary
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G-quadruplex resolution: From molecular mechanisms to physiological relevance DNA Repair (IF 3.8) Pub Date : 2023-08-03 Koichi Sato, Puck Knipscheer
Guanine-rich DNA sequences can fold into stable four-stranded structures called G-quadruplexes or G4s. Research in the past decade demonstrated that G4 structures are widespread in the genome and prevalent in regulatory regions of actively transcribed genes. The formation of G4s has been tightly linked to important biological processes including regulation of gene expression and genome maintenance