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微小染色体维持蛋白:从DNA复制到DNA损伤反应

Minichromosome Maintenance Proteins: From DNA Replication to the DNA Damage Response.

作者信息

Malysa Agnes, Zhang Xiaohong Mary, Bepler Gerold

机构信息

Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, 4100 John R Street, Detroit, MI 48201, USA.

出版信息

Cells. 2024 Dec 26;14(1):12. doi: 10.3390/cells14010012.

DOI:10.3390/cells14010012
PMID:39791713
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11719910/
Abstract

The DNA replication machinery is highly conserved from bacteria to eukaryotic cells. Faithful DNA replication is vital for cells to transmit accurate genetic information to the next generation. However, both internal and external DNA damages threaten the intricate DNA replication process, leading to the activation of the DNA damage response (DDR) system. Dysfunctional DNA replication and DDR are a source of genomic instability, causing heritable mutations that drive cancer evolutions. The family of minichromosome maintenance (MCM) proteins plays an important role not only in DNA replication but also in DDR. Here, we will review the current strides of MCM proteins in these integrated processes as well as the acetylation/deacetylation of MCM proteins and the value of MCMs as biomarkers in cancer.

摘要

从细菌到真核细胞,DNA复制机制高度保守。准确的DNA复制对于细胞向下一代传递精确的遗传信息至关重要。然而,内部和外部的DNA损伤都会威胁到复杂的DNA复制过程,从而导致DNA损伤反应(DDR)系统的激活。功能失调的DNA复制和DDR是基因组不稳定的一个来源,会导致驱动癌症进展的可遗传突变。微小染色体维持(MCM)蛋白家族不仅在DNA复制中起重要作用,在DDR中也发挥重要作用。在此,我们将综述MCM蛋白在这些整合过程中的最新进展,以及MCM蛋白的乙酰化/去乙酰化情况,以及MCM作为癌症生物标志物的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb1/11719910/cd9446604f1a/cells-14-00012-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb1/11719910/9126c62b9184/cells-14-00012-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb1/11719910/cd9446604f1a/cells-14-00012-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb1/11719910/9126c62b9184/cells-14-00012-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb1/11719910/cd9446604f1a/cells-14-00012-g002a.jpg

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Commun Biol. 2024 Feb 9;7(1):167. doi: 10.1038/s42003-024-05855-w.
2
Pan-Cancer Multi-Omics Analysis of Minichromosome Maintenance Proteins (MCMs) Expression in Human Cancers.人类癌症中微小染色体维持蛋白(MCMs)表达的泛癌多组学分析
Front Biosci (Landmark Ed). 2023 Sep 27;28(9):230. doi: 10.31083/j.fbl2809230.
3
Structural and mechanistic insights into the MCM8/9 helicase complex.
MCM8/9 解旋酶复合物的结构与机制研究进展
Elife. 2023 Aug 3;12:RP87468. doi: 10.7554/eLife.87468.
4
Looping out of control: R-loops in transcription-replication conflict.失控的循环:转录-复制冲突中的 R 环。
Chromosoma. 2024 Jan;133(1):37-56. doi: 10.1007/s00412-023-00804-8. Epub 2023 Jul 7.
5
Solving the MCM paradox by visualizing the scaffold of CMG helicase at active replisomes.通过可视化 CMG 解旋酶在活跃复制体中的支架来解决 MCM 悖论。
Nat Commun. 2022 Oct 14;13(1):6090. doi: 10.1038/s41467-022-33887-5.
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MCM6 is a critical transcriptional target of YAP to promote gastric tumorigenesis and serves as a therapeutic target.MCM6 是 YAP 促进胃肿瘤发生的关键转录靶标,可作为治疗靶点。
Theranostics. 2022 Sep 6;12(15):6509-6526. doi: 10.7150/thno.75431. eCollection 2022.
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A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress.MCM8/9 解旋酶复合物在复制应激过程中维持叉完整性的多功能作用。
Nat Commun. 2022 Aug 30;13(1):5090. doi: 10.1038/s41467-022-32583-8.
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Over-Activation of Minichromosome Maintenance Protein 10 Promotes Genomic Instability in Early Stages of Breast Cancer.微染色体维持蛋白 10 的过度激活促进乳腺癌早期的基因组不稳定。
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Efficiency and equity in origin licensing to ensure complete DNA replication.确保完全复制 DNA 的原始许可中的效率和公平性。
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