a Laboratory of Molecular Gerontology , National Institute on Aging, National Institutes of Health , Baltimore , MD USA.
b Department of Chemistry and Biochemistry , Baylor University , Waco , TX , USA.
Cell Cycle. 2019 May;18(10):1047-1055. doi: 10.1080/15384101.2019.1609833. Epub 2019 May 5.
Several decades of research have identified Mcm10 hanging around the replisome making several critical contacts with a number of proteins but with no real disclosed function. Recently, the O'Donnell laboratory has been better able to map the interactions of Mcm10 with a larger Cdc45/GINS/MCM (CMG) unwinding complex placing it at the front of the replication fork. They have shown biochemically that Mcm10 has the impressive ability to strip off single-strand binding protein (RPA) and reanneal complementary DNA strands. This has major implications in controlling DNA unwinding speed as well as responding to various situations where fork reversal is needed. This work opens up a number of additional facets discussed here revolving around accessing the DNA junction for different molecular purposes within a crowded replisome. alt-NHEJ: Alternative Nonhomologous End-Joining; CC: Coli-Coil motif; CMG: Cdc45/GINS/MCM2-7; CMGM: Cdc45/GINS/Mcm2-7/Mcm10; CPT: Camptothecin; CSB: Cockayne Syndrome Group B protein; CTD: C-Terminal Domain; DSB: Double-Strand Break; DSBR: Double-Strand Break Repair; dsDNA: Double-Stranded DNA; GINS: san, Sld5-Psf1-Psf2-Psf3; HJ Dis: Holliday Junction dissolution; HJ Res: Holliday Junction resolution; HR: Homologous Recombination; ICL: Interstrand Cross-Link; ID: Internal Domain; MCM: Minichromosomal Maintenance; ND: Not Determined; NTD: N-Terminal Domain; PCNA: Proliferating Cell Nuclear Antigen; RPA: Replication Protein A; SA: Strand Annealing; SE: Strand Exchange; SEW: Steric Exclusion and Wrapping; ssDNA: Single-Stranded DNA; TCR: Transcription-Coupled Repair; TOP1: Topoisomerase.
几十年来的研究已经确定 Mcm10 围绕着复制体，与许多蛋白质进行了几次关键接触，但没有真正揭示其功能。最近，O'Donnell 实验室能够更好地绘制 Mcm10 与更大的 Cdc45/GINS/MCM（CMG）解旋复合物的相互作用图，将其放置在复制叉的前端。他们已经在生化水平上证明，Mcm10 具有令人印象深刻的能力，可以去除单链结合蛋白（RPA）并重新退火互补 DNA 链。这对控制 DNA 解旋速度以及应对需要叉反转的各种情况具有重大影响。这项工作开辟了许多其他方面的讨论，这些讨论围绕着在拥挤的复制体中为不同的分子目的访问 DNA 连接点展开。
alt-NHEJ：替代非同源末端连接；CC：螺旋-转角-螺旋 motif；CMG：Cdc45/GINS/MCM2-7；CMGM：Cdc45/GINS/Mcm2-7/Mcm10；CPT：喜树碱；CSB：Cockayne 综合征组 B 蛋白；CTD：C 末端结构域；DSB：双链断裂；DSBR：双链断裂修复；dsDNA：双链 DNA；GINS：s san、Sld5-Psf1-Psf2-Psf3；HJ Dis：霍利迪连接点溶解；HJ Res：霍利迪连接点分辨率；HR：同源重组；ICL：链间交联；ID：内部结构域；MCM：微小染色体维持；ND：未确定；NTD：N 末端结构域；PCNA：增殖细胞核抗原；RPA：复制蛋白 A；SA：链退火；SE：链交换；SEW：空间位阻排除和包裹；ssDNA：单链 DNA；TCR：转录偶联修复；TOP1：拓扑异构酶。
