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

Haiyun Gan, Albert Serra-Cardona, Xu Hua, Hui Zhou, Karim Labib, Chuanhe Yu, Zhiguo Zhang

Research output: Contribution to journalArticle

17 Scopus citations


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. How parental histone H3-H4 tetramers are transferred to replicating DNA strands for epigenetic inheritance remains largely unknown. Gan et al. show that parental H3-H4 tetramers bind to Mcm2, which travels along the leading-strand template, and are then transferred to the lagging strand by the Mcm2-Ctf4-Polα complex for nucleosome assembly.

Original languageEnglish (US)
Pages (from-to)140-151.e3
JournalMolecular Cell
Issue number1
StatePublished - Oct 4 2018
Externally publishedYes


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

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