2. Academic Validation
  3. SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM

SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM

  • Sci China Life Sci. 2024 Oct 24. doi: 10.1007/s11427-023-2600-0.
Hongguo Duan # 1,  Shuang Wang # 1,  Wen-Jie Shu 1,  Yongjia Tong 2,  Hai-Zhen Long 3,  Guohong Li 4,  Hai-Ning Du 5,  Meng-Jie Zhao 6
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Emergency Center, Zhongnan Hospital of Wuhan University, RNA Institute, Wuhan University, Wuhan, 430072, China.
  • 2 The Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China.
  • 3 Shenzhen Bay Laboratory, Shenzhen, 518083, China.
  • 4 Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, China.
  • 5 Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Emergency Center, Zhongnan Hospital of Wuhan University, RNA Institute, Wuhan University, Wuhan, 430072, China. hainingdu@whu.edu.cn.
  • 6 Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Emergency Center, Zhongnan Hospital of Wuhan University, RNA Institute, Wuhan University, Wuhan, 430072, China. mjzhao@whu.edu.cn.
  • # Contributed equally.
PMID: 39455502 DOI: 10.1007/s11427-023-2600-0
Abstract

The minichromosome maintenance complex (MCM) DNA helicase is an important replicative factor during DNA replication. The proper chromatin loading of MCM is a key step to ensure replication initiation during S phase. Because replication initiation is regulated by multiple biological cues, additional changes to MCM may provide better understanding towards this event. Here, we report that histidine methyltransferase SETD3 promotes DNA replication in a manner dependent on enzymatic activity. Nascent-strand Sequencing (NS-seq) shows that SETD3 regulates replication initiation, as depletion of SETD3 attenuates early replication origins firing. Biochemical studies reveal that SETD3 binds MCM mainly during S phase, which is required for the CDT1-mediated chromatin loading of MCM. This MCM loading relies on histidine-459 methylation (H459me) on MCM7 which is catalyzed by SETD3. Impairment of H459 methylation attenuates DNA synthesis and chromatin loading of MCM. Furthermore, we show that CDK2 phosphorylates SETD3 at Serine-21 during the G1/S phase, which is required for DNA replication and cell cycle progression. These findings demonstrate a novel mechanism by which SETD3 methylates MCM to regulate replication initiation.

Keywords

DNA replication; MCM; SETD3; histidine methylation; replication origin firing.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z