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Repair of single-strand DNA interruptions by redundant pathways and its implication in cellular sensitivity to DNA-damaging agents.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2003 Dec 01; Vol. 31 (23), pp. 7032-40. - Publication Year :
- 2003
-
Abstract
- Single-strand DNA interruptions (SSIs) are produced during the process of base excision repair (BER). Through biochemical studies, two SSI repair subpathways have been identified: a pathway mediated by DNA polymerase beta (Pol beta) and DNA ligase III (Lig III), and a pathway mediated by DNA polymerase delta/epsilon (Pol delta/epsilon) and DNA ligase I (Lig I). In addition, the existence of another pathway, mediated by Pol beta and DNA Lig I, has been suggested. Although each pathway may play a unique role in cellular DNA damage response, the functional implications of SSI repair by these three pathways are not clearly understood. To obtain a better understanding of the functional relevance of SSI repair by these pathways, we investigated the involvement of each pathway by monitoring the utilization of DNA ligases in cell-free extracts. Our results suggest that the majority of SSIs produced during the repair of alkylated DNA bases are repaired by the pathway mediated by Pol beta and either Lig I or Lig III, although some SSIs are repaired by Pol delta/epsilon and Lig I. At a cellular level, we found that Lig III over-expression increased the resistance of cells to DNA-damaging agents, while Lig I over-expression had little effect. Thus, repair pathways mediated by Lig III may have a role in the regulation of cellular sensitivity to DNA-damaging agents.
- Subjects :
- Adenosine Monophosphate metabolism
Alkylation drug effects
Aphidicolin pharmacology
Cell Survival drug effects
Cell-Free System
DNA Ligase ATP
DNA Polymerase II metabolism
DNA Polymerase III metabolism
DNA, Single-Stranded genetics
Humans
Methylnitronitrosoguanidine pharmacology
Microspheres
Plasmids genetics
Plasmids metabolism
Poly-ADP-Ribose Binding Proteins
Xenopus Proteins
DNA Damage drug effects
DNA Ligases metabolism
DNA Polymerase beta metabolism
DNA Repair
DNA, Single-Stranded metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 31
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 14627836
- Full Text :
- https://doi.org/10.1093/nar/gkg892