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

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

May 7, 2024 | Congcong Tian, Qin Zhang, Jing Jia, Jiaqi Zhou, Ziwei Zhang, Srinivasu Karrf, Juhang Jiang, Quinn Dickinson, Yuan Yao, Xiaorong Tang, Yuxin Huang, Ting Guo, Ziwei He, Zheng Liu, Yuan Gao, Xinran Yang, Yuchun Wu, Kui Ming Chan, Daqin Zhang, Junhong Han, Chuanhe Yu, and Haiyun Gan
The study investigates the role of DNA polymerase delta subunit Pol32 in the transfer of parental histone H3–H4 to the lagging strand during DNA replication. The authors demonstrate that deleting Pol32, a nonessential subunit of DNA polymerase delta, results in a predominant transfer of parental histone H3–H4 to the leading strand. Biochemical analyses show that Pol32 can bind histone H3–H4 both in vivo and in vitro. The interaction between Pol32 and parental histone H3–H4 is disrupted by mutations in the histone-binding domain of Mcm2, a subunit of the MCM helicase. These findings identify Pol32 as a critical histone chaperone downstream of Mcm2, mediating the transfer of parental histones to the lagging strand during DNA replication. The study also explores the interaction between Pol32 and Pol1, another DNA polymerase subunit, and shows that Pol32 functions as a chaperone for parental histone transfer. Additionally, the authors observe that Pol32 deletion leads to chromatin instability, further highlighting its importance in epigenetic inheritance.The study investigates the role of DNA polymerase delta subunit Pol32 in the transfer of parental histone H3–H4 to the lagging strand during DNA replication. The authors demonstrate that deleting Pol32, a nonessential subunit of DNA polymerase delta, results in a predominant transfer of parental histone H3–H4 to the leading strand. Biochemical analyses show that Pol32 can bind histone H3–H4 both in vivo and in vitro. The interaction between Pol32 and parental histone H3–H4 is disrupted by mutations in the histone-binding domain of Mcm2, a subunit of the MCM helicase. These findings identify Pol32 as a critical histone chaperone downstream of Mcm2, mediating the transfer of parental histones to the lagging strand during DNA replication. The study also explores the interaction between Pol32 and Pol1, another DNA polymerase subunit, and shows that Pol32 functions as a chaperone for parental histone transfer. Additionally, the authors observe that Pol32 deletion leads to chromatin instability, further highlighting its importance in epigenetic inheritance.
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[slides and audio] DNA polymerase delta governs parental histone transfer to DNA replication lagging strand