Xu Z, Feng J, Yu D, Huo Y, Ma X, Lam WH, Liu Z, Li XD, Ishibashi T, Dang S, Zhai Y

The replisome that replicates the eukaryotic genome consists of at least three engines: the Cdc45-MCM-GINS (CMG) helicase that separates duplex DNA at the replication fork and two DNA polymerases, one on each strand, that replicate the unwound DNA. Here, we determined a series of cryo-electron microscopy structures of a yeast ...

Read More

replisome comprising CMG, leading-strand polymerase Pol? and three accessory factors on a forked DNA. In these structures, Pol? engages or disengages with the motor domains of the CMG by occupying two alternative positions, which closely correlate with the rotational movement of the single-stranded DNA around the MCM pore. During this process, the polymerase remains stably coupled to the helicase using Psf1 as a hinge. This synergism is modulated by a concerted rearrangement of ATPase sites to drive DNA translocation. The Pol?-MCM coupling is not only required for CMG formation to initiate DNA replication but also facilitates the leading-strand DNA synthesis mediated by Pol?. Our study elucidates a mechanism intrinsic to the replisome that coordinates the activities of CMG and Pol? to negotiate any roadblocks, DNA damage, and epigenetic marks encountered during translocation along replication forks.

Date: Sep. 20, 2023

View in: Pubmed Google Scholar

245627