| View Larger Image | UV-induced RPA phosphorylation is increased in the absence of DNA polymerase @h and requires DNA-PK [An article from: DNA Repair] | Digitalby S. Cruet-Hennequart (Author), S. Coyne (Author), M.T. Glynn (Author), Oakley (Author)
| List Price: | $10.95 | | | Available: | Available for download now |
| | Binding: | Digital | | Publisher: | Elsevier | | Page Count: | 13 Pages | | Publication Date: | April 08, 2006 |
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This digital document is a journal article from DNA Repair, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.Description: Signaling from arrested replication forks plays a role in maintaining genome stability. We have investigated this process in xeroderma pigmentosum variant cells that carry a mutation in the POLH gene and lack functional DNA polymerase @h (pol@h). Pol@h is required for error-free bypass of UV-induced cyclobutane pyrimidine dimers; in the absence of pol@h in XPV cells, DNA replication is arrested at sites of UV-induced DNA damage, and mutagenic bypass of lesions is ultimately carried out by other, error-prone, DNA polymerases. The present study investigates whether pol@h expression influences the activation of a number of UV-induced DNA damage responses. In a stably transfected XPV cell line (TR30-9) in which active pol@h can be induced by addition of tetracycline, expression of pol@h determines the extent of DNA double-strand break formation following UV-irradiation. UV-induced phosphorylation of replication protein A (RPA), a key DNA-binding protein involved in DNA replication, repair and recombination, is increased in cells lacking pol@h compared to when pol@h is expressed in the same cell line. To identify the protein kinase responsible for increased UV-induced hyperphosphorylation of the p34 subunit of RPA, we have used NU7441, a specific small molecule inhibitor of DNA-PK. DNA-PK is necessary for RPA p34 hyperphosphorylation, but DNA-PK-mediated phosphorylation is not required for recruitment of RPA p34 into nuclear foci in response to UV-irradiation. The results demonstrate that activation of a UV-induced DNA damage response pathway, involving phosphorylation of RPA p34 by DNA-PK, is enhanced in cells lacking pol@h. |
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