Replication DNA polymerases, genome instability and cancer therapies.
Replication DNA polymerases, genome instability and cancer therapies.
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作者：
自从首次在高度突变的子宫内膜癌和结直肠癌中发现复制DNA聚合酶ϵ和δ催化亚基基因的核酸外切酶结构域突变以来，已经有十多年的时间了。从那时起，人们对POLD1和POLD1的研究兴趣显著增加。在这些里程碑式的癌症基因组测序研究之前，有充分的证据表明，复制DNA聚合酶的突变降低了它们的DNA合成准确性、它们的核酸外切酶活性或它们与其他因素的相互作用，可能会导致小鼠的突变增加、DNA损伤甚至肿瘤发生。最近有几篇关于复制DNA聚合酶的评论，写得很好。该综述的目的是收集和较详细地综述DNA聚合酶ϵ和δ的最新研究，因为它们与基因组不稳定、癌症和潜在的治疗方法有关。这里的重点主要是最近关于编码其催化亚单位(POLE和POLD1)的基因突变的重要性、突变特征、相关基因的突变、模式生物以及化疗和免疫检查点抑制在聚合酶突变肿瘤中的应用的最新研究。
It has been over a decade since the initial identification of exonuclease domain mutations in the genes encoding the catalytic subunits of replication DNA polymerases ϵ and δ (POLE and POLD1) in tumors from highly mutated endometrial and colorectal cancers. Interest in studying POLE and POLD1 has increased significantly since then. Prior to those landmark cancer genome sequencing studies, it was well documented that mutations in replication DNA polymerases that reduced their DNA synthesis accuracy, their exonuclease activity or their interactions with other factors could lead to increased mutagenesis, DNA damage and even tumorigenesis in mice. There are several recent, well-written reviews of replication DNA polymerases. The aim of this review is to gather and review in some detail recent studies of DNA polymerases ϵ and δ as they pertain to genome instability, cancer and potential therapeutic treatments. The focus here is primarily on recent informative studies on the significance of mutations in genes encoding their catalytic subunits (POLE and POLD1), mutational signatures, mutations in associated genes, model organisms, and the utility of chemotherapy and immune checkpoint inhibition in polymerase mutant tumors.
影响因子：
10.5
作者：
Meng, Xiangzhou;Claussin, Clemence;Regan-Mochrie, Gemma;Whitehouse, Iestyn;Zhao, Xiaolan
通讯作者：
Zhao, Xiaolan
影响因子：
3.8
作者：
Zhou, Zhi-Xiong;Kunkel, Thomas A.
通讯作者：
Kunkel, Thomas A.