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A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks

Huang, Hongda ; Strømme, Caroline B. ; Saredi, Giulia LU ; Hödl, Martina ; Strandsby, Anne ; González-Aguilera, Cristina ; Chen, Shoudeng ; Groth, Anja and Patel, Dinshaw J. (2015) In Nature Structural and Molecular Biology 22(8). p.618-626
Abstract

During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones... (More)

During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling histones genome wide during DNA replication.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Structural and Molecular Biology
volume
22
issue
8
pages
9 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:26167883
  • scopus:84938692151
ISSN
1545-9993
DOI
10.1038/nsmb.3055
language
English
LU publication?
no
id
c2b134ed-c293-4043-b0ed-dbd9a57ec55a
date added to LUP
2025-11-03 11:18:40
date last changed
2025-11-03 11:33:25
@article{c2b134ed-c293-4043-b0ed-dbd9a57ec55a,
  abstract     = {{<p>During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling histones genome wide during DNA replication.</p>}},
  author       = {{Huang, Hongda and Strømme, Caroline B. and Saredi, Giulia and Hödl, Martina and Strandsby, Anne and González-Aguilera, Cristina and Chen, Shoudeng and Groth, Anja and Patel, Dinshaw J.}},
  issn         = {{1545-9993}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  pages        = {{618--626}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Structural and Molecular Biology}},
  title        = {{A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks}},
  url          = {{http://dx.doi.org/10.1038/nsmb.3055}},
  doi          = {{10.1038/nsmb.3055}},
  volume       = {{22}},
  year         = {{2015}},
}