机构：[1]Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.[2]Department of Biotherapy, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China.四川大学华西医院[3]Hormel Institute, University of Minnesota, Austin, MN 55912.[4]College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China.[5]Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, China.[6]School of Life Sciences, Henan University, Kaifeng 475004, China.[7]Shenzhen Research Institute of Henan University, Shenzhen 518000, China.[8]Kobilka Institute of Innovative Drug Discovery, School of Medicine, Chinese University of Hong Kong, Shenzhen 518172, China.[9]Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.[10]Pathology and Pathophysiology Basic Medical School, Qingdao University, Qindao 266000, China.[11]Department of Biomedical Sciences, City University of Hong Kong, Hong Kong Special Administration Region, China.[12]Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen 518172, China.[13]Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305.
Chromatin replication is intricately intertwined with the recycling of parental histones to the newly duplicated DNA strands for faithful genetic and epigenetic inheritance. The transfer of parental histones occurs through two distinct pathways: leading strand deposition, mediated by the DNA polymerase ε subunits Dpb3/Dpb4, and lagging strand deposition, facilitated by the MCM helicase subunit Mcm2. However, the mechanism of the facilitation of Mcm2 transferring parental histones to the lagging strand while moving along the leading strand remains unclear. Here, we show that the deletion of Pol32, a nonessential subunit of major lagging-strand DNA polymerase δ, results in a predominant transfer of parental histone H3-H4 to the leading strand during replication. Biochemical analyses further demonstrate that Pol32 can bind histone H3-H4 both in vivo and in vitro. The interaction of Pol32 with parental histone H3-H4 is disrupted through the mutation of the histone H3-H4 binding domain within Mcm2. Our findings identify the DNA polymerase δ subunit Pol32 as a critical histone chaperone downstream of Mcm2, mediating the transfer of parental histones to the lagging strand during DNA replication.
基金：
National Key R&D Program of China (2023YFA0913400 to H.G.), the Major Program of the National Natural Science Foundation of China (32090031 to H.G.), the Strategic
Priority Research Program of the Chinese Academy of Sciences (XDB0480000 to H.G.), the General Program of the National Natural Science Foundation of China
(32070610 to H.G.), NIH grant R01GM130588 (to C.Y.), the Hormel Startup Fund (to
C.Y.), the National Natural Science Foundation of China for Young Scholars (32100460
to J.Z. and 32101178 to Y.Y.), the Guangdong Province Fund for Distinguished Young
Scholars (2021B1515020109 to H.G.), Shenzhen Institute of Synthetic Biology
Scientific Research Program (JCHZ20200005, DWKF20210001, ZTXM20190019
to H.G.), Shenzhen Medical Research Funds (B2302049 to H.G.).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Tian Congcong,Zhang Qin,Jia Jing,et al.DNA polymerase delta governs parental histone transfer to DNA replication lagging strand[J].Proceedings Of The National Academy Of Sciences Of The United States Of America.2024,121(20):e2400610121.doi:10.1073/pnas.2400610121.
APA：
Tian Congcong,Zhang Qin,Jia Jing,Zhou Jiaqi,Zhang Ziwei...&Gan Haiyun.(2024).DNA polymerase delta governs parental histone transfer to DNA replication lagging strand.Proceedings Of The National Academy Of Sciences Of The United States Of America,121,(20)
MLA：
Tian Congcong,et al."DNA polymerase delta governs parental histone transfer to DNA replication lagging strand".Proceedings Of The National Academy Of Sciences Of The United States Of America 121..20(2024):e2400610121
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