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The DNA repair protein NBS1 influences the base excision repair pathway
- Source :
- Carcinogenesis 30, 408-415 (2009)
- Publication Year :
- 2009
- Publisher :
- Oxford University Press (OUP), 2009.
-
Abstract
- NBS1 fulfills important functions for the maintenance of genomic stability and cellular survival. Mutations in the NBS1 (Nijmegen Breakage Syndrome 1) gene are responsible for the Nijmegen breakage syndrome (NBS) in humans. The symptoms of this disease and the phenotypes of NBS1-defective cells, especially their enhanced radiosensitivity, can be explained by an impaired DNA double-strand break-induced signaling and a disturbed repair of these DNA lesions. We now provide evidence that NBS1 is also important for cellular survival after oxidative or alkylating stress where it is required for the proper initiation of base excision repair (BER). NBS1 downregulated cells show reduced activation of poly-(adenosine diphosphate-ribose)-polymerase-1 (PARP1) following genotoxic treatment with H(2)O(2) or methyl methanesulfonate, indicating impaired processing of damaged bases by BER as PARP1 activity is stimulated by the single-strand breaks intermediately generated during this repair pathway. Furthermore, extracts of these cells have a decreased capacity for the in vitro repair of a double-stranded oligonucleotide containing either uracil or 8-oxo-7,8-dihydroguanine to trigger BER. Our data presented here highlight for the first time a functional role for NBS1 in DNA maintenance by the BER pathway.
- Subjects :
- Cancer Research
Guanine
Alkylation
DNA Repair
Cell Survival
DNA repair
Poly (ADP-Ribose) Polymerase-1
Cell Cycle Proteins
Biology
Genomic Instability
chemistry.chemical_compound
DNA Maintenance
DNA Repair Protein
medicine
Humans
DNA Breaks, Double-Stranded
Uracil
strand break repair
werner-syndrome protein
ataxia-telangiectasia cells
poly(adp-ribose) polymerase-1
mre11/rad50/nbs1 complex
alzheimers-disease
damage
glycosylase
parp-1
mre11
Cells, Cultured
Nuclear Proteins
Hydrogen Peroxide
General Medicine
Base excision repair
DNA repair protein XRCC4
Methyl Methanesulfonate
medicine.disease
Molecular biology
Methyl methanesulfonate
Cell biology
Oxidative Stress
chemistry
Poly(ADP-ribose) Polymerases
Nijmegen breakage syndrome
DNA Damage
Signal Transduction
Nucleotide excision repair
Subjects
Details
- ISSN :
- 14602180 and 01433334
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....0adc6add5a5a4d975465d56ec841aaed
- Full Text :
- https://doi.org/10.1093/carcin/bgp004