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Mol Cell. 2018 Oct 4;72(1):140-151.e3. doi: 10.1016/j.molcel.2018.09.001. Epub 2018 Sep 20.

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

Author information

1
Institute for Cancer Genetics, Department of Pediatrics and Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
2
MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
3
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: yu.chuanhe@mayo.edu.
4
Institute for Cancer Genetics, Department of Pediatrics and Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: zz2401@cumc.columbia.edu.

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-Polα 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 Polα primase mutants that disrupt the connection of the CMG helicase to Polα 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-Polα complex to lagging-strand DNA for nucleosome assembly at the original location.

KEYWORDS:

Ctf4; DNA replication; Mcm2; Pol1; epigenetic inheritance; histone modifications; nucleosome assembly; parental histone transfer

PMID:
30244834
PMCID:
PMC6193272
[Available on 2019-10-04]
DOI:
10.1016/j.molcel.2018.09.001
[Indexed for MEDLINE]
Free PMC Article

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