共 72 条
Perinuclear Cohibin Complexes Maintain Replicative Life Span via Roles at Distinct Silent Chromatin Domains
被引:66
作者:
Chan, Janet N. Y.
[1
]
Poon, Betty P. K.
[1
]
Salvi, Jayesh
[1
]
Olsen, Jonathan B.
[2
,3
]
Emili, Andrew
[2
,3
]
Mekhail, Karim
[1
,4
]
机构:
[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Dept Mol Genet, Banting & Best Dept Med Res, Toronto, ON M5S 1A8, Canada
[3] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 1A8, Canada
[4] Univ Toronto, Fac Med, Canada Res Chairs Program, Toronto, ON M5S 1A8, Canada
基金:
加拿大健康研究院;
关键词:
INNER NUCLEAR-MEMBRANE;
YEAST SACCHAROMYCES-CEREVISIAE;
STRAND BREAK REPAIR;
BLOCK PROTEIN FOB1;
BUDDING YEAST;
RIBOSOMAL DNA;
TELOMERIC HETEROCHROMATIN;
MEDIATED REPRESSION;
SIR4;
PROTEINS;
RENT COMPLEX;
D O I:
10.1016/j.devcel.2011.05.014
中图分类号:
Q2 [细胞生物学];
学科分类号:
071013 [干细胞生物学];
摘要:
Heterochromatin, or silent chromatin, preferentially resides at the nuclear envelope. Telomeres and rDNA repeats are the two major perinuclear silent chromatin domains of Saccharomyces cerevisiae. The Cohibin protein complex maintains rDNA repeat stability in part through silent chromatin assembly and perinuclear rDNA anchoring. We report here a role for Cohibin at telomeres and show that functions of the complex at chromosome ends and rDNA maintain replicative life span. Cohibin binds LEM/SUN domain-containing nuclear envelope proteins and telomere-associated factors. Disruption of Cohibin or the envelope proteins abrogates telomere localization and silent chromatin assembly within subtelomeres. Loss of Cohibin limits Sir2 histone deacetylase localization to chromosome ends, disrupts subtelomeric DNA stability, and shortens life span even when rDNA repeats are stabilized. Restoring telomeric Sir2 concentration abolishes chromatin and life span defects linked to the loss of telomeric Cohibin. Our work uncovers roles for Cohibin complexes and reveals relationships between nuclear compartmentalization, chromosome stability, and aging.
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页码:867 / 879
页数:13
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