Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA.
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA.
DNA Repair (Amst). 2020 Sep;93:102918. doi: 10.1016/j.dnarep.2020.102918.
DNA mismatch repair (MMR) maintains genomic stability primarily by correcting replication errors. Defects in MMR lead to cancers and cause resistance to many chemotherapeutic drugs. Emerging evidence reveals that MMR is coupled with replication and precisely regulated in the context of chromatin; strikingly, tumors defective in MMR are highly responsive to immune checkpoint blockade therapy. As a tribute to Dr. Samuel Wilson for his many scientific contributions to the field of DNA repair and his leadership as Editor-in-Chief of the journal DNA Repair, we summarize recent developments in research on MMR at the chromatin level, its implications for tumorigenesis, and its therapeutic potential.
DNA 错配修复 (MMR) 主要通过纠正复制错误来维持基因组稳定性。MMR 的缺陷会导致癌症,并导致许多化疗药物产生耐药性。新出现的证据表明,MMR 与复制相关联,并在染色质的背景下得到精确调控;引人注目的是,MMR 缺陷的肿瘤对免疫检查点阻断治疗高度敏感。为了向 Dr. Samuel Wilson 对 DNA 修复领域的众多科学贡献以及作为该杂志 DNA 修复主编的领导表示敬意,我们总结了染色质水平上 MMR 研究的最新进展、其对肿瘤发生的影响及其治疗潜力。