The Mcm2-Ctf4-Pol? Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands.

ABSTRACT: Although essential for epigenetic inheritance, the transfer of parental histone (H3-H4)2 tetramers that contain epigenetic modifications to replicating DNA strands is poorly understood. Here, we show that the Mcm2-Ctf4-Pol? axis facilitates the transfer of parental (H3-H4)2 tetramers to lagging-strand DNA at replication forks. Mutating the conserved histone-binding domain of the Mcm2 subunit of the CMG (Cdc45-MCM-GINS) DNA helicase, which translocates along the leading-strand template, results in a marked enrichment of parental (H3-H4)2 on leading strand, due to the impairment of the transfer of parental (H3-H4)2 to lagging strands. Similar effects are observed in Ctf4 and Pol? primase mutants that disrupt the connection of the CMG helicase to Pol? that resides on lagging-strand template. Our results support a model whereby parental (H3-H4)2 complexes displaced from nucleosomes by DNA unwinding at replication forks are transferred by the CMG-Ctf4-Pol? complex to lagging-strand DNA for nucleosome assembly at the original location.

SUBMITTER: Gan H 

PROVIDER: S-EPMC6193272 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature