Genomic integrity of the cell is crucial for the successful transmission of genetic information to the offspring and its survival. Persistent DNA damage induced by endogenous and exogenous agents leads to various metabolic manifestations. To combat this, eukaryotes have developed complex DNA damage response (DDR) pathway which senses the DNA damage and activates an arsenal of enzymes for the repair of damaged DNA. The active pathways for DNA repair are nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR) for single-strand break repair whereas homologous recombination (HR) and non-homologous end-joining (NHEJ) for double-strand break repair. OGG1 is a DNA glycosylase which initiates BER while Mre11-Rad50-Nbs1 (MRN) protein complex is the primary responder to DSBs which gets localized to damage sites. DNA damage response is meticulously executed by three related kinases: ATM, ATR, and DNA-PK. ATM- and ATR-dependent phosphorylation of p53, Chk1, and Chk2 regulate the G1/S, intra-S, or G2/M checkpoints of the cell cycle, respectively. Autophagy is an evolutionarily conserved process that plays a pivotal role in the regulation of DNA repair and maintains the cellular homeostasis. Genotoxic stress-induced altered autophagy occurs in a P53 dependent manner which is also the master regulator of genotoxic stress. A plethora of proteins involved in autophagy is regulated by p53 which involve DRAM, DAPK, and AMPK. As evident, the mtDNA is more prone to damage than nuclear DNA because of its close proximity to the site of ROS generation. Depending on the extent of damage either the repair mechanism or mitophagy gets triggered. SIRT1 is the master regulator which directs the stress response to mitophagy. Nix, a LC3 adapter also participates in Parkin mediated mitophagy. This review highlights the intricate crosstalks between DNA damage and cell cycle checkpoints activation. The DNA damage mediated regulation of autophagy and mitophagy is also reviewed in detail.

中文翻译：

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细胞周期检查点和自噬在维持基因组完整性方面的牢固作用。

细胞的基因组完整性对于成功地将遗传信息传递给后代及其生存至关重要。内源性和外源性试剂诱导的持久性DNA损伤会导致各种代谢表现。为了克服这个问题，真核生物开发了复杂的DNA损伤反应（DDR）途径，该途径可以检测DNA损伤并激活酶库来修复受损的DNA。DNA修复的主动途径是单链断裂修复的核苷酸切除修复（NER），碱基切除修复（BER）和错配修复（MMR），而双链的同源重组（HR）和非同源末端连接（NHEJ） -钢绞线断裂修复。OGG1是一种DNA糖基化酶，可启动BER，而Mre11-Rad50-Nbs1（MRN）蛋白复合物是DSB的主要响应者，而DSB则位于受损部位。DNA损伤反应由三种相关的激酶精心执行：ATM，ATR和DNA-PK。p53，Chk1和Chk2的ATM和ATR依赖性磷酸化分别调节细胞周期的G1 / S，S内或G2 / M检查点。自噬是一种进化上保守的过程，在调节DNA修复和维持细胞稳态方面起着关键作用。遗传毒性应激诱导的自噬改变以P53依赖性方式发生，这也是遗传毒性应激的主要调节因子。p53调控涉及自噬的大量蛋白质，其中涉及DRAM，DAPK和AMPK。显然，由于mtDNA靠近ROS产生位点，因此它比核DNA更容易受到破坏。根据损坏的程度，修复机制或线粒体都会被触发。SIRT1是主调节器，可将应激反应引导至线粒体。Nix，一种LC3衔接子，也参与了Parkin介导的线粒体吞噬。这篇评论强调了DNA损伤与细胞周期检查点激活之间的错综复杂的串扰。DNA损伤介导的自噬和线粒体吞噬的调节也进行了详细的审查。