Caldecott K W
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brigton BN1 9RQ, United Kingdom.
DNA Repair (Amst). 2014 Jul;19:108-13. doi: 10.1016/j.dnarep.2014.03.021. Epub 2014 Apr 20.
DNA strand breaks arise continuously in cells and can lead to chromosome rearrangements and genome instability or cell death. The commonest DNA breaks are DNA single-strand breaks, which arise at a frequency of tens-of-thousands per cell each day and which can block the progression of RNA/DNA polymerases and disrupt gene transcription and genome duplication. If not rapidly repaired, SSBs can be converted into DNA double-strand breaks (DSBs) during genome duplication, eliciting a complex series of DNA damage responses that attempt to protect cells from irreversible replication fork collapse. DSBs are the most cytotoxic and clastogenic type of DNA breaks, and can also arise independently of DNA replication, albeit at a frequency several orders of magnitude lower than SSBs. Here, I discuss the evidence that DNA single- and double -strand break repair pathways, and cellular tolerance mechanisms for protecting replication forks during genome duplication, utilize signalling by protein ADP-ribosyltransferases to protect cells from the harmful impact of DNA strand breakage.
DNA链断裂在细胞中持续发生，可导致染色体重排和基因组不稳定，甚至细胞死亡。最常见的DNA断裂是DNA单链断裂，其每天在每个细胞中以数万次的频率出现，可阻断RNA/DNA聚合酶的进程，破坏基因转录和基因组复制。如果不迅速修复，单链断裂在基因组复制过程中可转化为DNA双链断裂（DSB），引发一系列复杂的DNA损伤反应，试图保护细胞免受不可逆的复制叉崩溃。双链断裂是最具细胞毒性和致染色体断裂性的DNA断裂类型，也可独立于DNA复制而产生，尽管其频率比单链断裂低几个数量级。在此，我将讨论相关证据，即DNA单链和双链断裂修复途径，以及基因组复制过程中保护复制叉的细胞耐受机制，利用蛋白质ADP-核糖基转移酶的信号传导来保护细胞免受DNA链断裂的有害影响。
