Department of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Department of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
DNA Repair (Amst). 2022 Oct;118:103383. doi: 10.1016/j.dnarep.2022.103383. Epub 2022 Aug 2.
Accurate DNA repair is essential for cellular and organismal homeostasis, and DNA repair defects result in genetic diseases and cancer predisposition. Several environmental factors, such as ultraviolet light, damage DNA, but many other molecules with DNA damaging potential are byproducts of normal cellular processes. In this review, we highlight some of the prominent sources of endogenous DNA damage as well as their mechanisms of repair, with a special focus on repair by the homologous recombination and Fanconi anemia pathways. We also discuss how modulating DNA damage caused by endogenous factors may augment current approaches used to treat BRCA-deficient cancers. Finally, we describe how synthetic lethal interactions may be exploited to exacerbate DNA repair deficiencies and cause selective toxicity in additional types of cancers.
准确的 DNA 修复对于细胞和机体的稳态至关重要，而 DNA 修复缺陷会导致遗传疾病和癌症易感性。紫外线等一些环境因素会破坏 DNA，但许多其他具有 DNA 损伤潜力的分子是正常细胞过程的副产品。在这篇综述中，我们重点介绍了一些主要的内源性 DNA 损伤来源及其修复机制，特别关注同源重组和范可尼贫血途径的修复。我们还讨论了如何调节内源性因素引起的 DNA 损伤，以增强目前用于治疗 BRCA 缺陷型癌症的方法。最后，我们描述了如何利用合成致死相互作用来加剧 DNA 修复缺陷，并在其他类型的癌症中引起选择性毒性。
