Human SIRT1 associates with mitotic chromatin and contributes to chromosomal condensation

被引:25
作者
Fatoba, Samuel T. [1 ]
Okorokov, Andrei L. [1 ]
机构
[1] UCL, Wolfson Inst Biomed Res, London, England
关键词
mitosis; SIRT1; chromosome condensation; deacetylation; aneuploidy; aging; HISTONE DEACETYLASE; XENOPUS-LAEVIS; CELL-CYCLE; SEGREGATION; MITOSIS; CANCER; IDENTIFICATION; INSTABILITY; SIRTUINS; INSIGHTS;
D O I
10.4161/cc.10.14.15913
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
SIRT1 is a NAD-dependent deacetylase that participates in cellular controls of gene expression, metabolism, genomic stability and anti-aging. Here we report that SIRT1 levels rise in prometaphase leading to SIRT1 global association with mitotic chromatin until telophase. Moreover, SIRT1 contributes to chromosomal condensation by mediating chromosomal loading of histone H1 and the condensin I complex. Consistently, SIRT1 knockdown led to improper condensation and overall aberrant mitosis. Our data highlight new role for SIRT1 in maintenance of chromosome stability in mitosis and suggests how diminished SIRT1 activity during aging and tumorigenesis may lead to aneuploidy and genomic instability.
引用
收藏
页码:2317 / 2322
页数:6
相关论文
共 30 条
[1]   Mitotic chromosome structure and condensation [J].
Belmont, Andrew S. .
CURRENT OPINION IN CELL BIOLOGY, 2006, 18 (06) :632-638
[2]   The Sir2 family of protein deacetylases [J].
Blander, G ;
Guarente, L .
ANNUAL REVIEW OF BIOCHEMISTRY, 2004, 73 :417-435
[3]  
Bode Ann M, 2005, Sci STKE, V2005, pre4, DOI 10.1126/stke.2812005re4
[4]   OPINION γH2AX and cancer [J].
Bonner, William M. ;
Redon, Christophe E. ;
Dickey, Jennifer S. ;
Nakamura, Asako J. ;
Sedelnikova, Olga A. ;
Solier, Stephanie ;
Pommier, Yves .
NATURE REVIEWS CANCER, 2008, 8 (12) :957-967
[5]   How does SIRT1 affect metabolism, senescence and cancer? [J].
Brooks, Christopher L. ;
Gu, Wei .
NATURE REVIEWS CANCER, 2009, 9 (02) :123-128
[6]   Histone hyperacetylation in mitosis prevents sister chromatid separation and produces chromosome segregation defects [J].
Cimini, D ;
Mattiuzzo, M ;
Torosantucci, L ;
Degrassi, F .
MOLECULAR BIOLOGY OF THE CELL, 2003, 14 (09) :3821-3833
[7]   Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle [J].
Dryden, SC ;
Nahhas, FA ;
Nowak, JE ;
Goustin, AS ;
Tainsky, MA .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (09) :3173-3185
[8]   Functional interplay between Parp-1 and SirT1 in genome integrity and chromatin-based processes [J].
El Ramy, Rosy ;
Magroun, Najat ;
Messadecq, Nadia ;
Gauthier, Laurent R. ;
Boussin, Francois D. ;
Kolthur-Seetharam, Ullas ;
Schreiber, Valerie ;
McBurney, Michael W. ;
Sassone-Corsi, Paolo ;
Dantzer, Francoise .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2009, 66 (19) :3219-3234
[9]   Recent progress in the biology and physiology of sirtuins [J].
Finkel, Toren ;
Deng, Chu-Xia ;
Mostoslavsky, Raul .
NATURE, 2009, 460 (7255) :587-591
[10]   Histone H1 and its isoforms: Contribution to chromatin structure and function [J].
Happel, Nicole ;
Doenecke, Detlef .
GENE, 2009, 431 (1-2) :1-12