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

Abstract

Here, we report that 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. In this paper we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L 1, 2, 3, 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 post-replicative 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. Finally, 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.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ;  [1];  [2];  [2];  [2];  [2]
  1. UCopenhagen
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
FOREIGN
OSTI Identifier:
1330254
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature; Journal Volume: 534; Journal Issue: 7609
Country of Publication:
United States
Language:
ENGLISH
Subject:
X-ray crystallography; Histone post-translational modifications

Citation Formats

Saredi, Giulia, Huang, Hongda, Hammond, Colin M., Alabert, Constance, Bekker-Jensen, Simon, Forne, Ignasi, Reverón-Gómez, Nazaret, Foster, Benjamin M., Mlejnkova, Lucie, Bartke, Till, Cejka, Petr, Mailand, Niels, Imhof, Axel, Patel, Dinshaw J., Groth, Anja, MSKCC), ICL), LMU), and Zurich). H4K20me0 marks post-replicative chromatin and recruits the TONSL₋MMS22L DNA repair complex. United States: N. p., 2016. Web. doi:10.1038/nature18312.
Saredi, Giulia, Huang, Hongda, Hammond, Colin M., Alabert, Constance, Bekker-Jensen, Simon, Forne, Ignasi, Reverón-Gómez, Nazaret, Foster, Benjamin M., Mlejnkova, Lucie, Bartke, Till, Cejka, Petr, Mailand, Niels, Imhof, Axel, Patel, Dinshaw J., Groth, Anja, MSKCC), ICL), LMU), & Zurich). H4K20me0 marks post-replicative chromatin and recruits the TONSL₋MMS22L DNA repair complex. United States. doi:10.1038/nature18312.
Saredi, Giulia, Huang, Hongda, Hammond, Colin M., Alabert, Constance, Bekker-Jensen, Simon, Forne, Ignasi, Reverón-Gómez, Nazaret, Foster, Benjamin M., Mlejnkova, Lucie, Bartke, Till, Cejka, Petr, Mailand, Niels, Imhof, Axel, Patel, Dinshaw J., Groth, Anja, MSKCC), ICL), LMU), and Zurich). 2016. "H4K20me0 marks post-replicative chromatin and recruits the TONSL₋MMS22L DNA repair complex". United States. doi:10.1038/nature18312.
@article{osti_1330254,
title = {H4K20me0 marks post-replicative chromatin and recruits the TONSL₋MMS22L DNA repair complex},
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 and MSKCC) and ICL) and LMU) and Zurich)},
abstractNote = {Here, we report that 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. In this paper we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L1, 2, 3, 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 post-replicative 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. Finally, 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.},
doi = {10.1038/nature18312},
journal = {Nature},
number = 7609,
volume = 534,
place = {United States},
year = 2016,
month = 6
}
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