Proliferative potential after DNA damage and non-homologous end joining are affected by loss of securin

被引：34

作者：

Bernal, J. A. ^{[1
,2
]}

Roche, M. ^{[2
]}

Mendez-Vidal, C. ^{[1
]}

Espina, A. ^{[1
]}

Tortolero, M. ^{[3
]}

Pintor-Toro, J. A. ^{[1
]}

机构：

[1] CABIMER, Ctr Andaluz Biol Mol & Med Regenerat, Seville 41092, Spain

[2] Hutchison MRC, Canc Cell Unit, Cambridge, England

[3] Univ Seville, Fac Biol, Dept Microbiol, E-41080 Seville, Spain

来源：

CELL DEATH AND DIFFERENTIATION | 2008年 / 15卷 / 01期

关键词：

double-strand breaks; genotoxic stress; NHEJ; securin; genomic stability;

D O I：

10.1038/sj.cdd.4402254

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

aThe faithful repair of DNA damage, especially chromosomal double-strand breaks (DSBs), is crucial for genomic integrity. We have previously shown that securin interacts with the Ku70/80 heterodimer of the DSB non-homologous DNA end-joining (NHEJ) repair machinery. Here we demonstrate that securin deficiency compromises cell survival and proliferation, but only after genotoxic stress. Securin(-/-) cells show a significant increase in gross chromosomal rearrangements and chromatid breaks after DNA damage, and also reveal an altered pattern of end resection in an NHEJ assay in comparison with securin(+/+) cells. These data suggest that securin has a key role in the maintenance of genomic stability after DNA damage, thereby providing a previously unknown mechanism for regulating tumour progression.

引用

页码：202 / 212

页数：11

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