MCM10在基因组复制中起着至关重要的作用,对于DNA复制启动至关重要,伸长率,和终止。它协调几种蛋白质在分叉处组装,形成功能复制体,触发原点展开,并稳定复制气泡。MCM10过表达与乳腺侵袭性增加有关,子宫颈,和其他几种癌症。MCM10的破坏导致与起始位点的增加和丢失相关的复制时机改变,并伴有基因组的不稳定性。敲除MCM10影响癌细胞的增殖和迁移,表现为DNA损伤和复制叉阻滞,最近被证明与CNKD和RCM等临床病症有关。MCM10功能的丧失与端粒酶活性受损有关,导致异常复制叉的积累和端粒长度受损。MCM10与组蛋白相互作用,有助于核小体组装,结合BRCA2在DNA损伤期间保持基因组完整性,防止病变跳跃,并抑制PRIMPOL介导的再灌注。它还与叉逆转酶SMARCAL1相互作用并抑制叉回归。此外,MCM10经历了几个翻译后修饰,并通过与SIR蛋白相互作用而有助于转录沉默。这篇综述探讨了与MCM10在DNA复制起始中的多方面作用相关的机制。染色质组织,转录沉默,复制应力,叉稳定性,端粒长度保持,和DNA损伤反应。最后,我们讨论了MCM10在癌症早期检测中的作用,其预后意义,及其在癌症治疗中的潜在用途。
MCM10 plays a vital role in genome duplication and is crucial for DNA replication initiation, elongation, and termination. It coordinates several proteins to assemble at the fork, form a functional replisome, trigger origin unwinding, and stabilize the replication bubble. MCM10 overexpression is associated with increased aggressiveness in breast, cervical, and several other cancers. Disruption of MCM10 leads to altered replication timing associated with initiation site gains and losses accompanied by genome instability. Knockdown of MCM10 affects the proliferation and migration of cancer cells, manifested by DNA damage and replication fork arrest, and has recently been shown to be associated with clinical conditions like CNKD and RCM. Loss of MCM10 function is associated with impaired telomerase activity, leading to the accumulation of abnormal replication forks and compromised telomere length. MCM10 interacts with histones, aids in nucleosome assembly, binds BRCA2 to maintain genome integrity during DNA damage, prevents lesion skipping, and inhibits PRIMPOL-mediated repriming. It also interacts with the fork reversal enzyme SMARCAL1 and inhibits fork regression. Additionally, MCM10 undergoes several post-translational modifications and contributes to transcriptional silencing by interacting with the SIR proteins. This review explores the mechanism associated with MCM10\'s multifaceted role in DNA replication initiation, chromatin organization, transcriptional silencing, replication stress, fork stability, telomere length maintenance, and DNA damage response. Finally, we discuss the role of MCM10 in the early detection of cancer, its prognostic significance, and its potential use in therapeutics for cancer treatment.