Back
Full-text
Journal article

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

  • Saredi G Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Huang H Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
  • Hammond CM Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Alabert C Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Bekker-Jensen S The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark.
  • Forne I Department of Molecular Biology, Biomedical Center and Center for Integrated Protein Science Munich, Ludwig-Maximilians University, Munich, Germany.
  • Reverón-Gómez N Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Foster BM MRC Clinical Sciences Centre, Imperial College London, United Kingdom.
  • Mlejnkova L Institute of Molecular Cancer Research, University of Zurich, Switzerland.
  • Bartke T MRC Clinical Sciences Centre, Imperial College London, United Kingdom.
  • Cejka P Institute of Molecular Cancer Research, University of Zurich, Switzerland.
  • Mailand N The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark.
  • Imhof A Department of Molecular Biology, Biomedical Center and Center for Integrated Protein Science Munich, Ludwig-Maximilians University, Munich, Germany.
  • Patel DJ Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
  • Groth A Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Show more…
  • 2016-06-25
Published in:
  • Nature. - 2016
Chromatin
DNA Repair
DNA Replication
DNA-Binding Proteins
Genomic Instability
Histones
Homologous Recombination
Humans
Lysine
Methylation
Models, Molecular
Molecular Chaperones
NF-kappa B
Nuclear Proteins
Protein Binding
Protein Structure, Tertiary
English 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 post-replicative chromatin, read by the human TONSL–MMS22L 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. 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/263540
Statistics
Document views: 58 File downloads:
  • Full-text: 0