文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

NAT10 介导的 MORC2 乙酰化调控乳腺癌细胞周期检查点控制和对 DNA 损伤化疗和放疗的抵抗。

Acetylation of MORC2 by NAT10 regulates cell-cycle checkpoint control and resistance to DNA-damaging chemotherapy and radiotherapy in breast cancer.

机构信息

Fudan University Shanghai Cancer Center and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Cancer Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China.

出版信息

Nucleic Acids Res. 2020 Apr 17;48(7):3638-3656. doi: 10.1093/nar/gkaa130.

DOI:10.1093/nar/gkaa130
PMID:32112098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7144926/
Abstract

MORC family CW-type zinc finger 2 (MORC2) is an oncogenic chromatin-remodeling enzyme with an emerging role in DNA repair. Here, we report a novel function for MORC2 in cell-cycle checkpoint control through an acetylation-dependent mechanism. MORC2 is acetylated by the acetyltransferase NAT10 at lysine 767 (K767Ac) and this process is counteracted by the deacetylase SIRT2 under unperturbed conditions. DNA-damaging chemotherapeutic agents and ionizing radiation stimulate MORC2 K767Ac through enhancing the interaction between MORC2 and NAT10. Notably, acetylated MORC2 binds to histone H3 phosphorylation at threonine 11 (H3T11P) and is essential for DNA damage-induced reduction of H3T11P and transcriptional repression of its downstream target genes CDK1 and Cyclin B1, thus contributing to DNA damage-induced G2 checkpoint activation. Chemical inhibition or depletion of NAT10 or expression of an acetylation-defective MORC2 (K767R) forces cells to pass through G2 checkpoint, resulting in hypersensitivity to DNA-damaging agents. Moreover, MORC2 acetylation levels are associated with elevated NAT10 expression in clinical breast tumor samples. Together, these findings uncover a previously unrecognized role for MORC2 in regulating DNA damage-induced G2 checkpoint through NAT10-mediated acetylation and provide a potential therapeutic strategy to sensitize breast cancer cells to DNA-damaging chemotherapy and radiotherapy by targeting NAT10.

摘要

MORC 家族 CW 型锌指 2（MORC2）是一种致癌性染色质重塑酶，在 DNA 修复中具有新兴作用。在这里，我们通过依赖于乙酰化的机制报告了 MORC2 在细胞周期检查点控制中的新功能。MORC2 在赖氨酸 767（K767Ac）处被乙酰转移酶 NAT10 乙酰化，并且在未受干扰的条件下，该过程被去乙酰化酶 SIRT2 抵消。DNA 损伤化学治疗药物和电离辐射通过增强 MORC2 和 NAT10 之间的相互作用来刺激 MORC2 K767Ac。值得注意的是，乙酰化的 MORC2 与组蛋白 H3 第 11 位苏氨酸（H3T11P）的磷酸化结合，并且对于 DNA 损伤诱导的 H3T11P 减少和其下游靶基因 CDK1 和 Cyclin B1 的转录抑制是必需的，从而有助于 DNA 损伤诱导的 G2 检查点激活。NAT10 的化学抑制或耗尽或表达乙酰化缺陷型 MORC2（K767R）迫使细胞通过 G2 检查点，导致对 DNA 损伤剂的敏感性增加。此外，MORC2 乙酰化水平与临床乳腺癌样本中 NAT10 表达的升高相关。总之，这些发现揭示了 MORC2 通过 NAT10 介导的乙酰化在调节 DNA 损伤诱导的 G2 检查点中的先前未被认识的作用，并提供了一种通过靶向 NAT10 使乳腺癌细胞对 DNA 损伤性化学疗法和放射疗法敏感的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/16f00bfabb85/gkaa130fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/538f460af93b/gkaa130fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/6177911578f5/gkaa130fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/b53fa36870f8/gkaa130fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/0c94aab43b29/gkaa130fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/75877b6c3837/gkaa130fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/b6d776aaa80d/gkaa130fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/f6be51346dad/gkaa130fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/97464783f7a6/gkaa130fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/a2a562e2f9b7/gkaa130fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/16f00bfabb85/gkaa130fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/538f460af93b/gkaa130fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/6177911578f5/gkaa130fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/b53fa36870f8/gkaa130fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/0c94aab43b29/gkaa130fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/75877b6c3837/gkaa130fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/b6d776aaa80d/gkaa130fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/f6be51346dad/gkaa130fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/97464783f7a6/gkaa130fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/a2a562e2f9b7/gkaa130fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/7144926/16f00bfabb85/gkaa130fig10.jpg

相似文献

[1]
Acetylation of MORC2 by NAT10 regulates cell-cycle checkpoint control and resistance to DNA-damaging chemotherapy and radiotherapy in breast cancer.

Nucleic Acids Res. 2020-4-17

[2]
MORC2 regulates DNA damage response through a PARP1-dependent pathway.

Nucleic Acids Res. 2019-9-19

[3]
Poly(ADP-ribosyl)ation of acetyltransferase NAT10 by PARP1 is required for its nucleoplasmic translocation and function in response to DNA damage.

Cell Commun Signal. 2022-8-19

[4]
Dynamic SUMOylation of MORC2 orchestrates chromatin remodelling and DNA repair in response to DNA damage and drives chemoresistance in breast cancer.

Theranostics. 2023

[5]
Destabilization of microrchidia family CW-type zinc finger 2 via the cyclin-dependent kinase 1-chaperone-mediated autophagy pathway promotes mitotic arrest and enhances cancer cellular sensitivity to microtubule-targeting agents.

Clin Transl Med. 2023-3

[6]
Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair.

Cell Commun Signal. 2019-12-3

[7]
[Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell].

Zhonghua Zhong Liu Za Zhi. 2022-6-23

[8]
Histone acetylation and the cell-cycle in cancer.

Front Biosci. 2001-4-1

[9]
Estrogen receptor β causes a G2 cell cycle arrest by inhibiting CDK1 activity through the regulation of cyclin B1, GADD45A, and BTG2.

Breast Cancer Res Treat. 2010-12-1

[10]
UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53.

J Natl Cancer Inst. 1996-7-17

引用本文的文献

[1]
Research progress on NAT10-mediated acetylation in normal development and disease.

Front Cell Dev Biol. 2025-8-13

[2]
Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.

Cancer Drug Resist. 2025-7-21

[3]
Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.

Signal Transduct Target Ther. 2025-7-18

[4]
Mechanistic study of N-acetyltransferase 10 deficiency enhancing olaparib sensitivity in triple negative breast cancer by inhibiting RAD51 N4-acetylcytidine modification.

iScience. 2025-6-9

[5]
Bioinformatics identification and validation of m6A/m1A/m5C/m7G/ac4 C-modified genes in oral squamous cell carcinoma.

BMC Cancer. 2025-7-1

[6]
Emerging role of N-acetyltransferase 10 in diseases: RNA ac4C modification and beyond.

Mol Biomed. 2025-7-1

[7]
Comparison of transcriptome profiles of radiotherapy beams on MCF-7 breast cancer xenografts.

Breast Cancer. 2025-6-27

[8]
NAT10 promotes hepatocellular carcinoma progression by modulating the ac4C-DDIAS-PI3K-Akt axis.

Sci Rep. 2025-5-19

[9]
Deacetylation of ANXA2 by SIRT2 desensitizes hepatocellular carcinoma cells to donafenib via promoting protective autophagy.

Cell Death Differ. 2025-5-3

[10]
NAT10 promotes gastric cancer progression by enhancing the N4-acetylcytidine modification of TNC mRNA.

Infect Agent Cancer. 2025-3-29

本文引用的文献

[1]
MORC2 regulates DNA damage response through a PARP1-dependent pathway.

Nucleic Acids Res. 2019-9-19

[2]
RNF144A functions as a tumor suppressor in breast cancer through ubiquitin ligase activity-dependent regulation of stability and oncogenic functions of HSPA2.

Cell Death Differ. 2020-3

[3]
N-Acetyltransferase 10 Enhances Doxorubicin Resistance in Human Hepatocellular Carcinoma Cell Lines by Promoting the Epithelial-to-Mesenchymal Transition.

Oxid Med Cell Longev. 2019-7-1

[4]
PARP1 regulates DNA damage-induced nucleolar-nucleoplasmic shuttling of WRN and XRCC1 in a toxicant and protein-specific manner.

Sci Rep. 2019-7-11

[5]
MORC2 regulates C/EBPα-mediated cell differentiation via sumoylation.

Cell Death Differ. 2019-1-15

[6]
Characterization of molecular mechanisms underlying the axonal Charcot-Marie-Tooth neuropathy caused by MORC2 mutations.

Hum Mol Genet. 2019-5-15

[7]
Functions and mechanisms of non-histone protein acetylation.

Nat Rev Mol Cell Biol. 2019-3

[8]
Acetylation of Cytidine in mRNA Promotes Translation Efficiency.

Cell. 2018-11-15

[9]
dbPTM in 2019: exploring disease association and cross-talk of post-translational modifications.

Nucleic Acids Res. 2019-1-8

[10]
MORC2 promotes development of an aggressive colorectal cancer phenotype through inhibition of NDRG1.

Cancer Sci. 2018-12-21

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索