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H4K20me0 marks post-replicative chromatin and recruits the TONSL-MMS22L DNA repair complex

Saredi, Giulia LU ; Huang, Hongda ; Hammond, Colin M. ; Alabert, Constance ; Bekker-Jensen, Simon ; Forne, Ignasi ; Reverón-Gómez, Nazaret ; Foster, Benjamin M. ; Mlejnkova, Lucie and Bartke, Till , et al. (2016) In Nature 534(7609). p.714-718
Abstract

After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal that new histones incorporated during DNA replication provide a signature of postreplicative chromatin, read by the human TONSL-MMS22L1-4 homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replication and mark postreplicative chromatin until the G2/M phase of the cell cycle. Accordingly,... (More)

After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal that new histones incorporated during DNA replication provide a signature of postreplicative chromatin, read by the human TONSL-MMS22L1-4 homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replication and mark postreplicative chromatin until the G2/M phase of the cell cycle. Accordingly, TONSL-MMS22L binds new histones H3-H4 both before and after incorporation into nucleosomes, remaining on replicated chromatin until late G2/M. H4K20me0 recognition is required for TONSL-MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Together, these data reveal a histone-reader-based mechanism for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy.

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publishing date
type
Contribution to journal
publication status
published
in
Nature
volume
534
issue
7609
pages
714 - 718
publisher
Nature Publishing Group
external identifiers
  • scopus:85011377139
  • pmid:27338793
ISSN
0028-0836
DOI
10.1038/nature18312
language
English
LU publication?
no
additional info
Publisher Copyright: © 2016 Macmillan Publishers Limited. All rights reserved.
id
8df320c4-fabe-402a-ac44-9f97f44760ea
date added to LUP
2025-11-03 11:18:00
date last changed
2025-11-17 14:18:24
@article{8df320c4-fabe-402a-ac44-9f97f44760ea,
  abstract     = {{<p>After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal that new histones incorporated during DNA replication provide a signature of postreplicative chromatin, read by the human TONSL-MMS22L1-4 homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replication and mark postreplicative chromatin until the G2/M phase of the cell cycle. Accordingly, TONSL-MMS22L binds new histones H3-H4 both before and after incorporation into nucleosomes, remaining on replicated chromatin until late G2/M. H4K20me0 recognition is required for TONSL-MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Together, these data reveal a histone-reader-based mechanism for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy.</p>}},
  author       = {{Saredi, Giulia and Huang, Hongda and Hammond, Colin M. and Alabert, Constance and Bekker-Jensen, Simon and Forne, Ignasi and Reverón-Gómez, Nazaret and Foster, Benjamin M. and Mlejnkova, Lucie and Bartke, Till and Cejka, Petr and Mailand, Niels and Imhof, Axel and Patel, Dinshaw J. and Groth, Anja}},
  issn         = {{0028-0836}},
  language     = {{eng}},
  number       = {{7609}},
  pages        = {{714--718}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature}},
  title        = {{H4K20me0 marks post-replicative chromatin and recruits the TONSL-MMS22L DNA repair complex}},
  url          = {{http://dx.doi.org/10.1038/nature18312}},
  doi          = {{10.1038/nature18312}},
  volume       = {{534}},
  year         = {{2016}},
}