DNA polymerase delta governs parental histone transfer to DNA replication lagging strand

Congcong Tian (Co-first Author), Qin Zhang (Co-first Author), Jing Jia (Co-first Author), Jiaqi Zhou (Co-first Author), Ziwei Zhang (Co-first Author), Srinivasu Karri, Jiuhang Jiang, Quinn Dickinson, Yuan Yao, Xiaorong Tang, Yuxin Huang, Ting Guo, Ziwei He, Zheng Liu, Yuan Gao, Xinran Yang, Yuchun Wu, Kui Ming Chan, Daoqin Zhang, Junhong Han*Chuanhe Yu*, Haiyun Gan*

*Corresponding author for this work

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

11 Citations (Scopus)
27 Downloads (CityUHK Scholars)

Abstract

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.
Original languageEnglish
Article numbere2400610121
JournalProceedings of the National Academy of Sciences
Volume121
Issue number20
Online published7 May 2024
DOIs
Publication statusPublished - 14 May 2024

Funding

This work was supported by the following Fundings. 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.).

Research Keywords

  • DNA polymerase δ
  • epigenetic inheritance
  • histone chaperone
  • parental histone transfer
  • Pol32

Publisher's Copyright Statement

  • COPYRIGHT TERMS OF DEPOSITED FINAL PUBLISHED VERSION FILE: This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

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