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.
引用
收藏
页码:867 / 879
页数:13
相关论文
共 72 条
[1]
The nuclear envelope and transcriptional control [J].
Akhtar, Asifa ;
Gasser, Susan M. .
NATURE REVIEWS GENETICS, 2007, 8 (07) :507-517
[2]
Esc1, a nuclear periphery protein required for Sir4-based plasmid anchoring and partitioning [J].
Andrulis, ED ;
Zappulla, DC ;
Ansari, A ;
Perrod, S ;
Laiosa, CV ;
Gartenberg, MR ;
Sternglanz, R .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (23) :8292-8301
[3]
MODIFIERS OF POSITION EFFECT ARE SHARED BETWEEN TELOMERIC AND SILENT MATING-TYPE LOCI IN SACCHAROMYCES-CEREVISIAE [J].
APARICIO, OM ;
BILLINGTON, BL ;
GOTTSCHLING, DE .
CELL, 1991, 66 (06) :1279-1287
[4]
Telomeres and human disease: Ageing, cancer and beyond [J].
Blasco, MA .
NATURE REVIEWS GENETICS, 2005, 6 (08) :611-622
[5]
Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways [J].
Boulton, SJ ;
Jackson, SP .
EMBO JOURNAL, 1996, 15 (18) :5093-5103
[6]
Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast [J].
Bryk, M ;
Banerjee, M ;
Murphy, M ;
Knudsen, KE ;
Garfinkel, DJ ;
Curcio, MJ .
GENES & DEVELOPMENT, 1997, 11 (02) :255-269
[7]
ACTION OF A RAP1 CARBOXY-TERMINAL SILENCING DOMAIN REVEALS AN UNDERLYING COMPETITION BETWEEN HMR AND TELOMERES IN YEAST [J].
BUCK, SW ;
SHORE, D .
GENES & DEVELOPMENT, 1995, 9 (03) :370-384
[8]
Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3 [J].
Bupp, Jennifer M. ;
Martin, Adriana E. ;
Stensrud, Elizabeth S. ;
Jaspersen, Sue L. .
JOURNAL OF CELL BIOLOGY, 2007, 179 (05) :845-854
[9]
Human laminopathies: nuclei gone genetically awry [J].
Capell, Brian C. ;
Collins, Francis S. .
NATURE REVIEWS GENETICS, 2006, 7 (12) :940-952
[10]
MPS3 mediates meiotic bouquet formation in Saccharomyces cerevisiae [J].
Conrad, Michael N. ;
Lee, Chih-Ying ;
Wilkerson, Joseph L. ;
Dresser, Michael E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (21) :8863-8868