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DNA Damage Levels and Biochemical Repair Capacities Associated with XRCC1 Deficiency
- Source :
- Biochemistry. 44:14335-14343
- Publication Year :
- 2005
- Publisher :
- American Chemical Society (ACS), 2005.
-
Abstract
- Base excision repair (BER) is the major corrective pathway for most spontaneous, oxidative, and alkylation DNA base and sugar damage. X-ray cross-complementing 1 (XRCC1) has been suggested to function at nearly every step of this repair process, primarily through direct protein-protein interactions. Using whole cell extract (WCE) repair assays and DNA damage measurement techniques, we examined systematically the quantitative contribution of XRCC1 to specific biochemical steps of BER and single-strand break repair (SSBR). Our studies reveal that XRCC1-deficient Chinese hamster ovary WCEs exhibit normal base excision activity for 8-oxoguanine (8-OH-dG), 5-hydroxycytosine, ethenoadenine, and uracil lesions. Moreover, XRCC1 mutant EM9 cells possess steady-state levels of endogenous 8-OH-dG base damage similar to those of their wild-type counterparts. Abasic site incision activity was found to be normal in XRCC1-deficient cell extracts, as were the levels of abasic sites in isolated chromosomal DNA from mutant cells. While one- and five-nucleotide gap filling was not affected by XRCC1 status, a significant approximately 2-4-fold reduction in nick ligation activity was observed in EM9 WCEs. Our results herein suggest that the primary biochemical defect associated with XRCC1 deficiency is in the ligation step of BER/SSBR, and that XRCC1 plays no significant role in endogenous base damage and abasic site repair, or in promoting the polymerase gap-filling step.
- Subjects :
- Cell Extracts
Guanine
Time Factors
DNA Repair
DNA repair
DNA damage
Biology
Biochemistry
Cell Line
Cytosine
chemistry.chemical_compound
XRCC1
Cricetinae
Animals
AP site
Uracil
Binding Sites
Adenine
Ovary
Base excision repair
Molecular biology
DNA-Binding Proteins
X-ray Repair Cross Complementing Protein 1
chemistry
DNA glycosylase
Mutation
Female
DNA
DNA Damage
Nucleotide excision repair
Subjects
Details
- ISSN :
- 15204995 and 00062960
- Volume :
- 44
- Database :
- OpenAIRE
- Journal :
- Biochemistry
- Accession number :
- edsair.doi.dedup.....ecf57ad8cbc9b1235656901f7f5d935d