修复哺乳动物细胞周期 S 期的 DNA 链间交联。
Repair of DNA interstrand cross-links during S phase of the mammalian cell cycle.
机构信息
Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
出版信息
Environ Mol Mutagen. 2010 Jul;51(6):540-51. doi: 10.1002/em.20566.
Abstract
DNA interstrand cross-linking (ICL) agents are widely used in anticancer chemotherapy regimens, yet our understanding of the DNA repair mechanisms by which these lesions are removed from the genome remains incomplete. This is at least in part due to the enormously complicated nature and variety of the biochemical pathways that operate on these complex lesions. In this review, we have focused specifically on the S-phase pathway of ICL repair in mammalian cells, which appears to be the major mechanism by which these lesions are removed in cycling cells. The various stages and components of this pathway are discussed, and a putative molecular model is presented. In addition, we propose an explanation as to how this pathway can lead to the observed high levels of sister chromatid exchanges known to be induced by ICLs.
摘要
DNA 链间交联 (ICL) 试剂被广泛应用于癌症的化学疗法中，但我们对这些损伤从基因组中被清除的 DNA 修复机制的理解仍然不完整。这至少部分归因于作用于这些复杂损伤的生化途径的复杂性质和多样性。在这篇综述中，我们特别关注了哺乳动物细胞中 ICL 修复的 S 期途径，该途径似乎是在有丝分裂细胞中清除这些损伤的主要机制。本文讨论了该途径的各个阶段和组成部分，并提出了一个假设的分子模型。此外，我们还提出了一种解释，说明该途径如何导致已知由 ICL 诱导的高水平姐妹染色单体交换。
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