Methylation of UHRF1 by SET7 is essential for DNA double-strand break repair.
CCAAT-Enhancer-Binding Proteins
/ genetics
DNA Breaks, Double-Stranded
DNA Damage
/ genetics
DNA Methylation
/ genetics
DNA Repair
/ genetics
Heterochromatin
/ genetics
Histone Demethylases
/ genetics
Histone-Lysine N-Methyltransferase
/ genetics
Humans
Phosphorylation
Proliferating Cell Nuclear Antigen
/ genetics
Protein Binding
/ genetics
S Phase
/ genetics
Ubiquitin-Protein Ligases
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
10 01 2019
10 01 2019
Historique:
received:
16
07
2018
accepted:
06
10
2018
pubmed:
26
10
2018
medline:
23
8
2019
entrez:
26
10
2018
Statut:
ppublish
Résumé
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a key epigenetic regulator of DNA methylation maintenance and heterochromatin formation. The roles of UHRF1 in DNA damage repair also have been emphasized in recent years. However, the regulatory mechanism of UHRF1 remains elusive. In this study, we showed that UHRF1 is methylated by SET7 and demethylation is catalyzed by LSD1. In addition, methylation of UHRF1 is induced in response to DNA damage and its phosphorylation in S phase is a prerequisite for interaction with SET7. Furthermore, UHRF1 methylation catalyzes the conjugation of polyubiquitin chains to PCNA and promotes homologous recombination for DNA repair. SET7-mediated UHRF1 methylation is also shown to be essential for cell viability against DNA damage. Our data revealed the regulatory mechanism underlying the UHRF1 methylation status by SET7 and LSD1 in double-strand break repair pathway.
Identifiants
pubmed: 30357346
pii: 5144143
doi: 10.1093/nar/gky975
pmc: PMC6326791
doi:
Substances chimiques
CCAAT-Enhancer-Binding Proteins
0
Heterochromatin
0
Proliferating Cell Nuclear Antigen
0
Histone Demethylases
EC 1.14.11.-
KDM1A protein, human
EC 1.5.-
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
SETD7 protein, human
EC 2.1.1.43
UHRF1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
184-196Références
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