This review article discusses some insights about generating novel mechanistic inhibitors of the DNA damage response and repair (DDR) pathways by focusing on protein–protein interactions (PPIs) of the key DDR components. General requirements for PPI strategies, such as selecting the target PPI site on the basis of its functionality, are discussed first. Next, on the basis of functional rationale and biochemical feasibility to identify a PPI inhibitor, 26 PPIs in DDR pathways (BER, MMR, NER, NHEJ, HR, TLS, and ICL repair) are specifically discussed for inhibitor discovery to benefit cancer therapies using a DNA-damaging agent.

中文翻译：

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在DNA损伤反应和修复途径中靶向蛋白质-蛋白质相互作用的潜在策略

这篇评论文章讨论了有关通过关注关键DDR成分的蛋白质-蛋白质相互作用（PPI）来产生DNA损伤反应和修复（DDR）途径的新型机械抑制剂的一些见解。首先讨论了PPI策略的一般要求，例如根据其功能选择目标PPI站点。接下来，基于功能原理和生化可行性以识别PPI抑制剂，特别讨论了DDR通路中的26个PPI（BER，MMR，NER，NHEJ，HR，TLS和ICL修复），以发现抑制剂以利于使用PPI的癌症治疗DNA破坏剂。