DNA interstrand cross-links (ICLs) covalently connect the two strands of the double helix and are extremely cytotoxic. Defective ICL repair causes the bone marrow failure and cancer predisposition syndrome, Fanconi anemia, and upregulation of repair causes chemotherapy resistance in cancer. The central event in ICL repair involves resolving the cross-link (unhooking). In this review, we discuss the chemical diversity of ICLs generated by exogenous and endogenous agents. We then describe how proliferating and nonproliferating vertebrate cells unhook ICLs. We emphasize fundamentally new unhooking strategies, dramatic progress in the structural analysis of the Fanconi anemia pathway, and insights into how cells govern the choice between different ICL repair pathways. Throughout, we highlight the many gaps that remain in our knowledge of these fascinating DNA repair pathways. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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脊椎动物DNA链间交联修复的机制。

DNA链间交联（ICL）共价连接双螺旋的两条链，具有极强的细胞毒性。ICL修复缺陷会导致骨髓衰竭和癌症易感综合征，范科尼贫血，修复的上调会导致癌症对化疗的耐药性。ICL修复中的中心事件涉及解决交叉链接（脱钩）。在这篇综述中，我们讨论了由外源性和内源性物质产生的ICL的化学多样性。然后，我们描述增殖和不增殖的脊椎动物细胞如何解钩ICL。我们从根本上强调新的脱钩策略，在Fanconi贫血途径的结构分析中取得显着进展，并深入了解细胞如何控制不同ICL修复途径之间的选择。始终，我们着重指出了我们对这些引人入胜的DNA修复途径的认识中仍然存在的许多空白。《生物化学年度评论》第90卷的最终最终在线发布日期为2021年6月。请参阅http://www.annualreviews.org/page/journal/pubdates以获取修订的估算值。