Web of Science: 208 cites, Scopus: 225 cites, Google Scholar: cites,
The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation
Serrano, Lourdes (Department of Genetics, the Human Genetics Institute of New Jersey. Rutgers University)
Martínez-Redondo, Paloma (Institut d'Investigació Biomèdica de Bellvitge)
Marazuela Duque, Anna (Institut d'Investigació Biomèdica de Bellvitge)
Vazquez Prat, Berta Nieves (Department of Genetics, the Human Genetics Institute of New Jersey. Rutgers University)
Dooley, Scott J. (Department of Genetics, the Human Genetics Institute of New Jersey. Rutgers University)
Voigt, Philipp (Department of Biochemistry, New York University School of Medicine)
Beck, David B. (Department of Biochemistry, New York University School of Medicine)
Kane-Goldsmith, Noriko (Department of Genetics, the Human Genetics Institute of New Jersey. Rutgers University)
Tong, Qiang (Children's Nutrition Research Center)
Rabanal Prados, Rosa Ma. (Rosa Maria) (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Fondevila, Dolors (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Muñoz, Purificación (Institut d'Investigació Biomèdica de Bellvitge)
Krüger, Marcus (Max Planck Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Tischfield, Jay A. (Department of Genetics, the Human Genetics Institute of New Jersey. Rutgers University)
Vaquero, Alejandro (Institut d'Investigació Biomèdica de Bellvitge)

Data: 2013
Resum: The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1-3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: H4K20me1 ; PR-Set7 ; SIRT2 ; Epigenetics ; Genome instability ; Sirtuins
Publicat a: Genes & Development, 2013 , ISSN 1549-5477

DOI: 10.1101/gad.211342.112
PMID: 23468428


16 p, 3.8 MB

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