UV sensitivity and impaired nucleotide excision repair in DNA-dependent protein kinase mutant cells

Muller, C.; Calsou, P.; Frit, P.; Salles, B.; Cayrol, C.; Carter, T.

doi:10.1093/nar/26.6.1382

Cited by 51DNA Repair MechanismsNuclear Structure and FunctionDNA and Nucleic Acid Chemistry

UV sensitivity and impaired nucleotide excision repair in DNA-dependent protein kinase mutant cells

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Muller, C., Calsou, P., Frit, P., Salles, B., Cayrol, C., Carter, T.·1998·Nucleic Acids Research

DOI 10.1093/nar/26.6.1382PMC PMC147427

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Abstract

DNA-dependent protein kinase (DNA-PK), a member of the phosphatidyl-inositol (PI)3-kinase family, is involved in the repair of DNA double-strand breaks. Its regulatory subunit, Ku, binds to DNA and recruits the kinase catalytic subunit (DNA-PKcs). We show here a new role of DNA-PK in the modulation of the process of nucleotide excision repair (NER) in vivo since, as compared with their respective parental cell lines, DNA-PK mutants (scid , V-3 and xrs 6 cells) exhibit sensitivity to UV-C irradiation (2.0- to 2.5-fold) and cisplatin ( approximately 3- to 4-fold) associated with a decreased activity (40-55%) of unscheduled DNA synthesis after UV-C irradiation. Moreover, we observed that wortmannin sensitized parental cells in vivo when combined with either cisplatin or UV-C light, but had no effect on the DNA-PKcs deficient scid cells. Despite a lower repair synthesis activity (approximately 2-fold) measured in vitro with nuclear cell extracts from DNA-PK mutants, a direct involvement of DNA-PK in the NER reaction in vitro has not been observed. This study establishes a regulatory function of DNA-PK in the NER process in vivo but rules out a physical role of the complex in the repair machinery at the site of the DNA lesion.

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Cells lacking functional DNA-PK components have elevated sensitivity to UV irradiation.
“Cells lacking functional DNA-PK components are known to have elevated sensitivity toward UV irradiation [312].”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [312]

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UV sensitivity and impaired nucleotide excision repair in DNA-dependent protein kinase mutant celis. Nucleic Acids Res
Muller, C., Calsou, P., Cayrol, C., Carter, T., & Salles, B. (1998)
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Authors: Muller, C., Calsou, P., Frit, P., Salles, B., Cayrol, C., & Carter, T.
Affiliations: Centre National de la Recherche Scientifique (FR)
Hôpital Rangueil (FR)
St. John's University (US)
ORCID: Muller, C.
Calsou, P.
Frit, P.
Cayrol, C.
Venue: Nucleic Acids Research
Publisher: Oxford University Press (OUP)
Published: 1998-03-01
Volume: 26
Issue: 6
Pages: 1382-1389
ISSN: 0305-1048 (ISSN-L)
1362-4962
DOI: 10.1093/nar/26.6.1382
PMC: PMC147427
OpenAlex: W2039635928
Cited by: 51
References: 60
Citations by year: 2023: 1 · 2021: 1 · 2020: 2 · 2016: 1 · 2015: 1 · 2014: 2 · 2012: 3
FWCI: 1.98
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Nucleic Acids Research (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Association pour la Recherche sur le Cancer
Fondation de France
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords: DNA-dependent protein kinase, nucleotide excision repair, UV sensitivity, cisplatin sensitivity, Ku protein, DNA-PKcs, wortmannin, unscheduled DNA synthesis, PI3-kinase, DNA double-strand break repair, UV-C irradiation
MeSH terms: Wortmannin, Phosphoinositide-3 Kinase Inhibitors, Androstadienes, Animals, Bleomycin, Cell Line, Cell Survival, Cisplatin, DNA Repair, DNA-Binding Proteins, Enzyme Inhibitors, Cricetinae, HeLa Cells, Humans, Nuclear Proteins, Radiation Tolerance, Radiation-Sensitizing Agents, Ultraviolet Rays, CHO Cells, Mice, SCID, Protein Serine-Threonine Kinases, Mice, DNA-Activated Protein Kinase

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UV sensitivity and impaired nucleotide excision repair in DNA-dependent protein kinase mutant cells

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