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Molecular and Cellular Biology, April 2000, p. 2696-2705, Vol. 20, No. 8
Institut de Pharmacologie et de Biologie
Structurale, CNRS UPR 9062, F-31077 Toulouse Cedex,
France,1 and Department of
Biochemistry, University of Iowa, Iowa City, Iowa
52242-11092
Received 27 October 1999/Returned for modification 8 December
1999/Accepted 18 January 2000
Exposure of mammalian cells to short-wavelength light (UVC)
triggers a global response which can either counteract the deleterious effect of DNA damage by enabling DNA repair or lead to apoptosis. Several stress-activated protein kinases participate in this response, making phosphorylation a strong candidate for being involved in regulating the cellular damage response. One factor that is
phosphorylated in a UVC-dependent manner is the 32-kDa subunit of the
single-stranded DNA-binding replication protein A (RPA32). RPA is
required for major cellular processes like DNA replication, and removal
of DNA damage by nucleotide excision repair (NER). In this study we
examined the signal which triggers RPA32 hyperphosphorylation following UVC irradiation in human cells. Hyperphosphorylation of RPA
was observed in cells from patients with either NER or transcription-coupled repair (TCR) deficiency (A, C, and G
complementation groups of xeroderma pigmentosum and A and B groups of
Cockayne syndrome, respectively). This exclude both NER intermediates
and TCR as essential signals for RPA hyperphosphorylation. However, we
have observed that UV-sensitive cells deficient in NER and TCR require
lower doses of UV irradiation to induce RPA32 hyperphosphorylation than
normal cells, indicating that persistent unrepaired lesions contribute
to RPA phosphorylation. Finally, the results of UVC irradiation
experiments on nonreplicating cells and S-phase-synchronized cells
emphasize a major role for DNA replication arrest in the presence of
UVC lesions in RPA UVC-induced hyperphosphorylation in mammalian cells.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
DNA Replication but Not Nucleotide Excision Repair Is Required
for UVC-Induced Replication Protein A Phosphorylation in
Mammalian Cells
*
Corresponding author. Mailing address: Institut de
Pharmacologie et de Biologie Structurale, CNRS UPR 9062, 205 route de
Narbonne, F-31077 Toulouse Cedex, France. Phone: (33)-561-17-59-36. Fax (33)-561-17-59-33. E-mail: salles{at}ipbs.fr.
Molecular and Cellular Biology, April 2000, p. 2696-2705, Vol. 20, No. 8
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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