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

Zhang, W.; Xu, J.; Yang, J.; Shi, G.; Wu, J.; Gao, N.; Feng, J.; Li, Q.

2024-08-08 molecular biology
10.1101/2024.08.08.607175 bioRxiv
Show 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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