Telomeres are partly shielded from ultraviolet-induced damage and proficient for nucleotide excision repair of photoproducts.
Ultraviolet light induces cyclobutane pyrimidine dimers (CPD) and pyrimidine(6-4)pyrimidone photoproducts, which interfere with DNA replication and transcription. Nucleotide excision repair (NER) removes these photoproducts, but whether NER functions at telomeres is unresolved. Here we use immunospot blotting to examine the efficiency of photoproduct formation and removal at telomeres purified from UVC irradiated cells at various recovery times. Telomeres exhibit approximately twofold fewer photoproducts compared with the bulk genome in cells, and telomere-binding protein TRF1 significantly reduces photoproduct formation in telomeric fragments in vitro. CPD removal from telomeres occurs 1.5-fold faster than the bulk genome, and is completed by 48 h. 6-4PP removal is rapidly completed by 6 h in both telomeres and the overall genome. A requirement for XPA protein indicates the mechanism of telomeric photoproduct removal is NER. These data provide new evidence that telomeres are partially protected from ultraviolet irradiation and that NER preserves telomere integrity.
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Dhvani
D
Parikh
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.|University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
Elise
E
Fouquerel
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.|Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
Connor T
CT
Murphy
Department of Physics, North Carolina State University, Raleigh, NC 27695, USA.
Hong
H
Wang
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.|University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.|Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.|Department of Physics, North Carolina State University, Raleigh, NC 27695, USA.
Patricia L
PL
Opresko
D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D006801:Humans; D016615:Telomere / Q000528:radiation effects*; D014466:Ultraviolet Rays