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Poly(ADP-RIBOSE) polymerase-1 (Parp-1) antagonizes topoisomerase I-dependent recombination stimulation by P53
| Content Provider | Semantic Scholar |
|---|---|
| Author | Baumann, Cindy Boehden, Gisa S. Bürkle, Alexander Wiesmüller, Lisa |
| Copyright Year | 2006 |
| Abstract | PARP-1 interacts with and poly(ADP-ribosyl)ates p53 and topoisomerase I, which both participate in DNA recombination. Previously, we showed that PARP-1 downregulates homology-directed double-strand break (DSB) repair. We also discovered that, despite the well-established role of p53 as a global suppressor of error-prone recombination, p53 enhances homologous recombination (HR) at the RARalpha breakpoint cluster region (bcr) comprising topoisomerase I recognition sites. Using an SV40-based assay and isogenic cell lines differing in the p53 and PARP-1 status we demonstrate that PARP-1 counteracts HR enhancement by p53, although DNA replication was largely unaffected. When the same DNA element was integrated in an episomal recombination plasmid, both p53 and PARP-1 exerted anti-recombinogenic rather than stimulatory activities. Strikingly, with DNA substrates integrated into cellular chromosomes, enhancement of HR by p53 and antagonistic PARP-1 action was seen, very similar to the HR of viral minichromosomes. siRNA-mediated knockdown revealed the essential role of topoisomerase I in this regulatory mechanism. However, after I-SceI-meganuclease-mediated cleavage of the chromosomally integrated substrate, no topoisomerase I-dependent effects by p53 and PARP-1 were observed. Our data further indicate that PARP-1, probably through topoisomerase I interactions rather than poly(ADP-ribosyl)ation, prevents p53 from stimulating spontaneous HR on chromosomes via topoisomerase I activity. |
| Starting Page | 1036 |
| Ending Page | 1049 |
| Page Count | 14 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 16473854v1 |
| Volume Number | 34 |
| Journal | Nucleic acids research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenosine Diphosphate B-Cell Receptor Complex BCR gene Chromosomes DNA Breaks, Double-Stranded DNA Replication Homologous Gene PARP1 protein, human Poly(ADP-ribose) Polymerases Recombination, Genetic SCEI protein, S cerevisiae Stimulation (motivation) Topoisomerase II double-strand break repair via homologous recombination physical hard work topoisomerase activity |
| Content Type | Text |
| Resource Type | Article |
