FACT-(H3-H4) complex stimulates Pol activity to coordinate DNA synthesis with nucleosome assembly

Wenshuo Zhang; Geng Shichen; Jiawei Xu; Yuantao Tang; Guanzhong Jiao; Jin-qing Yang; Guojun Shi; Jiale Wu; Fangnan Qin; Ning Gao; Jianxun Feng; Qing Li

doi:10.1126/sciadv.aeh7889

Molecular BiologyScience AdvancesSep 25, 2026

Peer-reviewed journal article

FACT-(H3-H4) complex stimulates Pol activity to coordinate DNA synthesis with nucleosome assembly

Wenshuo Zhang iD, Geng Shichen iD, Jiawei Xu iD, Yuantao Tang iD, Guanzhong Jiao iD, Jin-qing Yang iD, Guojun Shi iD, Jiale Wu iD, Fangnan Qin iD, Ning Gao iD, Jianxun Feng iD, Qing Li iD

Abstract

Deficiencies in replication-coupled (RC) nucleosome assembly often lead to reduced DNA replication rate, but the precise mechanism underlying this process remains unsolved. Here, we discovered that H3-H4, but not H2A-H2B, mediates the interaction between FACT and the primase-polymerase complex DNA Pol . This interaction stimulates the DNA polymerase activity of Pol , and is indispensable for Okazaki fragment synthesis and replication fork progression. Moreover, the Pol1-N domain of Pol provides a specific binding site for FACT and H3-H4. Furthermore, CAF-1 and Rtt106-mediated replication-coupled nucleosome assembly pathways regulate this interaction. Together, we propose that the FACT-(H3-H4)-Pol interaction acts as a "Pre-Warning System" that regulates DNA replication, ensuring proper coordination between DNA synthesis and nucleosome assembly.

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