DNA double-strand break (DSB) resection, once thought to be a simple enzymatic process, is emerging as a highly complex series of coordinated activities required to maintain genome integrity. Progress in cell biology, biochemistry, and genetics has deciphered the precise resecting activities, the regulatory components, and their ability to properly channel the resected DNA to the appropriate DNA repair pathway. Herein, we review the mechanisms of regulation of DNA resection, with an emphasis on negative regulators that prevent single-strand (ss)DNA accumulation to maintain genome stability. Interest in targeting DNA resection inhibitors is emerging because their inactivation leads to poly(ADP-ribose) polymerase inhibitor (PARPi) resistance. We also present detailed regulation of DNA resection machineries, their analysis by functional assays, and their impact on disease and PARPi resistance.

DNA 双链断裂 (DSB) 切除曾经被认为是一个简单的酶促过程，现在正在成为维持基因组完整性所需的一系列高度复杂的协调活动。细胞生物学、生物化学和遗传学的进展已经破译了精确的切除活动、调节成分以及它们将切除的 DNA 正确引导到适当的 DNA 修复途径的能力。在此，我们回顾了 DNA 切除的调控机制，重点是防止单链 (ss) DNA 积累以维持基因组稳定性的负调控因子。对靶向 DNA 切除抑制剂的兴趣正在出现，因为它们的失活会导致聚（ADP-核糖）聚合酶抑制剂 (PARPi) 抗性。我们还介绍了 DNA 切除机器的详细规定，通过功能分析对其进行分析，