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
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
收藏
页码:202 / 212
页数:11
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