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bioRxiv · 10.1101/2024.08.08.607175

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.
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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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Zhang, W., Xu, J., Yang, J., Shi, G., Wu, J., Gao, N., Feng, J., Li, Q.. 2024-08-08. FACT-(H3-H4) complex stimulates Pol activity to coordinate DNA synthesis with nucleosome assembly. https://doi.org/10.1101/2024.08.08.607175

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