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 (Lead / Corresponding author), Zhiguo Zhang (Lead / Corresponding author)

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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. 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
Pages (from-to)140-151.e3
Number of pages16
JournalMolecular Cell
Volume72
Issue number1
Early online date20 Sep 2018
DOIs
Publication statusPublished - 4 Oct 2018

Fingerprint

Histones
Nucleosomes
Epigenomics
DNA
DNA Primase
DNA Helicases
DNA Replication

Keywords

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

Cite this

Gan, Haiyun ; Serra-Cardona, Albert ; Hua, Xu ; Zhou, Hui ; Labib, Karim ; Yu, Chuanhe ; Zhang, Zhiguo. / The Mcm2-Ctf4-Polα Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands. In: Molecular Cell. 2018 ; Vol. 72, No. 1. pp. 140-151.e3.
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Gan, H, Serra-Cardona, A, Hua, X, Zhou, H, Labib, K, Yu, C & Zhang, Z 2018, 'The Mcm2-Ctf4-Polα Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands', Molecular Cell, vol. 72, no. 1, pp. 140-151.e3. https://doi.org/10.1016/j.molcel.2018.09.001

The Mcm2-Ctf4-Polα Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands. / Gan, Haiyun; Serra-Cardona, Albert; Hua, Xu; Zhou, Hui; Labib, Karim; Yu, Chuanhe (Lead / Corresponding author); Zhang, Zhiguo (Lead / Corresponding author).

In: Molecular Cell, Vol. 72, No. 1, 04.10.2018, p. 140-151.e3.

Research output: Contribution to journalArticle

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T1 - The Mcm2-Ctf4-Polα Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands

AU - Gan, Haiyun

AU - Serra-Cardona, Albert

AU - Hua, Xu

AU - Zhou, Hui

AU - Labib, Karim

AU - Yu, Chuanhe

AU - Zhang, Zhiguo

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

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N2 - 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.

AB - 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.

KW - nucleosome assembly

KW - epigenetic inheritance

KW - DNA replication

KW - histone modifications

KW - Mcm2

KW - Ctf4

KW - Pol1

KW - parental histone transfer

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DO - 10.1016/j.molcel.2018.09.001

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