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

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-in...

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Bibliographic Details
Published in:DNA repair 2010-02, Vol.9 (2), p.161-168
Main Authors: Narine, Kelly A.D., Keuling, Angela M., Gombos, Randi, Tron, Victor A., Andrew, Susan E., Young, Leah C.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - radiation effects
Bacteriology
bcl-2-Associated X Protein - metabolism
Biological and medical sciences
Caspase 2
Caspase 2 - metabolism
Caspase 9 - metabolism
Cell Extracts
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cells, Cultured
Centrosome
Centrosome - enzymology
Centrosome - radiation effects
Cytochromes c - secretion
DNA mismatch repair
DNA Mismatch Repair - radiation effects
DNA-Binding Proteins - metabolism
Enzyme Activation - radiation effects
Fundamental and applied biological sciences. Psychology
Growth, nutrition, cell differenciation
Membrane Potential, Mitochondrial - radiation effects
Mice
Microbiology
Microscopy, Confocal
Mitochondria - enzymology
Mitochondria - radiation effects
Molecular and cellular biology
Molecular genetics
Msh6
Mutagenesis. Repair
MutS Homolog 2 Protein - metabolism
p53
Protein Transport - radiation effects
Receptors, Death Domain - metabolism
Signal Transduction - radiation effects
Subcellular Fractions - metabolism
Tumor Suppressor Protein p53 - metabolism
Ultraviolet Rays
UVB
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Summary: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.
ISSN:1568-7864
1568-7856
DOI:10.1016/j.dnarep.2009.11.010