Journal
DNA REPAIR
Volume 10, Issue 1, Pages 5-15Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2010.09.004
Keywords
UV damage; DNA double strand breaks; Xeroderma pigmentosum group B; Comet assay; Immunofluorescence; gamma-H2AX; Wip1
Categories
Funding
- U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, MD, USA
Ask authors/readers for more resources
DNA double strand breaks (DSB) may be caused by ionizing radiation. In contrast, UV exposure forms dipyrimidine photoproducts and is not considered an inducer of DSB. We found that uniform or localized UV treatment induced phosphorylation of the DNA damage related (DDR) proteins H2AX, ATM and NBS1 and co-localization of gamma-H2AX with the DDR proteins p-ATM, p-NBS1, Rad51 and FANCD2 that persisted for about 6 h in normal human fibroblasts. This post-UV phosphorylation was observed in the absence of nucleotide excision repair (NER), since NER deficient XP-B cells (lacking functional XPB DNA repair helicase) and global genome repair-deficient rodent cells also showed phosphorylation and localization of these DDR proteins. Resolution of the DDR proteins was dependent on NER, since they persisted for 24 h in the XP-B cells. In the normal and XP-B cells p53 and p21 was detected at 6 h and 24 h but Mdm2 was not induced in the XP-B cells. Post-UV induction of Wip1 phosphatase was detected in the normal cells but not in the XP-B cells. DNA DSB were detected with a neutral comet assay at 6 h and 24 h post-UV in the normal and XP-B cells. These results indicate that UV damage can activate the DDR pathway in the absence of NER. However, a later step in DNA damage processing involving induction of Wip1 and resolution of DDR proteins was not observed in the absence of NER. Published by Elsevier ay.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available