Regulation of DNA double-strand break repair pathway choice

脱氧核糖核酸双海滨裂缝(DSB ) 是能包括大规模或小规模的删除，杂合现象的损失， translocations，和染色体损失导致房间死亡或许多基因改变的批评损害。DSB 被修理由非相应加入结束(NHEJ ) 并且相应再结合(HR ) ，和在这些小径的缺点引起染色体不稳定性并且支持 tumorigenesis。DSB 包括直接或间接地损坏脱氧核糖核酸并且通常在癌症治疗被使用的离子辐射和化学药品包括在细胞的新陈代谢，折叠复制叉，和核酸酶期间产生的反应的氧种类从内长的来源，并且从外长的来源产生。DSB 修理小径看起来竞争因为在他们之间的 DSB，而是平衡在种之中广泛地不同，在单个种的不同细胞类型之间，并且在一个单身者的不同细胞周期阶段期间，细胞打字。这里，我们考察在酵母和更高的优核质由 NHEJ 和 HR 调整 DSB 修理的规章的因素。这些因素包括修理蛋白质，修理因素可接近性的染色质调整，和相应修理模板的可获得性的调整表示和磷酸化。当大多数 DSB 修理蛋白质看起来专门在 NHEJ 或 HR 工作时，很多蛋白质影响两条小径，包括 MRE11/RAD50/NBS1 (XRS2 ) 建筑群， BRCA1，嘘一 H2AX， PARP-1， RAD18， DNA 依赖的蛋白激酶催化子单元(DNA-PKcs ) ，和 ATM。DNA-PKcs 在哺乳动物的 NHEJ 起一个作用，但是它也通过可以与涉及是由 DNA-PKcs 的 phosphorylated 的 HR 的至少 12 蛋白质的 ATM 或 ATM 包含串音的一个复杂规章的网络影响 HR。

DNA double-strand breaks （DSBs） are critical lesions that can result in cell death or a wide variety of genetic alterations including largeor small-scale deletions, loss of heterozygosity, translocations, and chromosome loss. DSBs are repaired by non-homologous end-joining （NHEJ） and homologous recombination （HR）, and defects in these pathways cause genome instability and promote tumorigenesis. DSBs arise from endogenous sources including reactive oxygen species generated during cellular metabolism, collapsed replication forks, and nucleases, and from exogenous sources including ionizing radiation and chemicals that directly or indirectly damage DNA and are commonly used in cancer therapy. The DSB repair pathways appear to compete for DSBs, but the balance between them differs widely among species, between different cell types of a single species, and during different cell cycle phases of a single cell type. Here we review the regulatory factors that regulate DSB repair by NHEJ and HR in yeast and higher eukaryotes. These factors include regulated expression and phosphorylation of repair proteins, chromatin modulation of repair factor accessibility, and the availability of homologous repair templates. While most DSB repair proteins appear to function exclusively in NHEJ or HR, a number of proteins influence both pathways, including the MRE11/RAD50/NBS1（XRS2） complex, BRCA1, histone H2AX, PARP-1, RAD18, DNA-dependent protein kinase catalytic subunit （DNA-PKcs）, and ATM. DNA-PKcs plays a role in mammalian NHEJ, but it also influences HR through a complex regulatory network that may involve crosstalk with ATM, and the regulation of at least 12 proteins involved in HR that are phosphorylated by DNA-PKcs and/or ATM.