Defining the DNA mismatch repair-dependent apoptotic pathway in primary cells: Evidence for p53-independence and involvement of centrosomal caspase 2

被引:9
作者
Narine, Kelly A. D. [1 ]
Keuling, Angela M. [1 ]
Gombos, Randi [1 ]
Tron, Victor A. [2 ]
Andrew, Susan E. [1 ]
Young, Leah C. [1 ]
机构
[1] Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2H7, Canada
[2] Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada
基金
加拿大健康研究院;
关键词
DNA mismatch repair; Msh6; UVB; Apoptosis; p53; Caspase; 2; Centrosome; FEMALE EMBRYONIC LETHALITY; PROMOTER REGION; CYCLE ARREST; PROTEIN MSH6; CANCER CELLS; SKIN-CANCER; GENE HMSH2; IN-VIVO; P53; DAMAGE;
D O I
10.1016/j.dnarep.2009.11.010
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Many studies have shown that DNA mismatch repair (MMR) has a role beyond that of repair in response to several types of DNA damage, including ultraviolet radiation (UV). We have demonstrated previously that the MMR-dependent component of UVB-induced apoptosis is integral to the suppression of UVB-induced tumorigenesis. Here we demonstrate that Msh6-dependent UVB-induced apoptotic pathway is both activated via the mitochondria and p53-independent. In addition, we have shown for the first time that caspase 2, an initiator caspase, localizes to the centrosomes in mitotic primary mouse embryonic fibroblasts, irrespective of MMR status and UVB treatment. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:161 / 168
页数:8
相关论文
共 55 条
[1]   Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2 [J].
Adamson, AW ;
Beardsley, DI ;
Kim, WJ ;
Gao, YJ ;
Baskaran, R ;
Brown, KD .
MOLECULAR BIOLOGY OF THE CELL, 2005, 16 (03) :1513-1526
[2]   Mismatch repair in correction of replication errors and processing of DNA damage [J].
Aquilina, G ;
Bignami, M .
JOURNAL OF CELLULAR PHYSIOLOGY, 2001, 187 (02) :145-154
[3]   Functional interactions and signaling properties of mammalian DNA mismatch repair proteins [J].
Bellacosa, A .
CELL DEATH AND DIFFERENTIATION, 2001, 8 (11) :1076-1092
[4]   A guided tour into subcellular colocalization analysis in light microscopy [J].
Bolte, S. ;
Cordelieres, F. P. .
JOURNAL OF MICROSCOPY, 2006, 224 (213-232) :213-232
[5]   Msh2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect [J].
Campbell, MR ;
Wang, Y ;
Andrew, SE ;
Liu, Y .
ONCOGENE, 2006, 25 (17) :2531-2536
[6]  
CAMPBELL MR, DNA MISMATCH R UNPUB
[7]  
Caporali S, 2004, MOL PHARMACOL, V66, P478
[8]   Methylation-induced G2/M arrest requires a full complement of the mismatch repair protein hMLH1 [J].
Cejka, P ;
Stojic, L ;
Mojas, N ;
Russell, AM ;
Heinimann, K ;
Cannavó, E ;
di Pietro, M ;
Marra, G ;
Jiricny, J .
EMBO JOURNAL, 2003, 22 (09) :2245-2254
[9]   Prodomain-dependent nuclear localization of the caspase-2 (Nedd2) precursor - A novel function for a caspase prodomain [J].
Colussi, PA ;
Harvey, NL ;
Kumar, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (38) :24535-24542
[10]   Female embryonic lethality in mice nullizygous for both Msh2 and p53 [J].
Cranston, A ;
Bocker, T ;
Reitmair, A ;
Palazzo, J ;
Wilson, T ;
Mak, T ;
Fishel, R .
NATURE GENETICS, 1997, 17 (01) :114-118