Meiotic recombination provokes functional activation of the p53 regulatory network Journal Article
| Authors: | Lu, W. J.; Chapo, J.; Roig, I.; Abrams, J. M. |
| Article Title: | Meiotic recombination provokes functional activation of the p53 regulatory network |
| Abstract: | The evolutionary appearance of p53 protein probably preceded its role in tumor suppression, suggesting that there may be unappreciated functions for this protein. Using genetic reporters as proxies to follow in vivo activation of the p53 network in Drosophila, we discovered that the process of meiotic recombination instigates programmed activation of p53 in the germ line. Specifically, double-stranded breaks in DNA generated by the topoisomerase Spoil provoked functional p53 activity, which was prolonged in cells defective for meiotic DNA repair. This intrinsic stimulus for the p53 regulatory network is highly conserved because Spo11-dependent activation of p53 also occurs in mice. Our findings establish a physiological role for p53 in meiosis and suggest that tumor-suppressive functions may have been co-opted from primordial activities linked to recombination. |
| Keywords: | immunohistochemistry; dna-binding proteins; nonhuman; protein function; cytology; meiosis; animals; mice; mice, knockout; spermatocytes; dna damage; mus; dna repair; green fluorescent protein; protein; genotype; drosophila; in vivo study; enzyme activity; protein p53; physiology; embryo, nonmammalian; gene expression regulation, developmental; germ cells; germ line; dna; genetic recombination; recombination, genetic; dna breaks, double-stranded; tumor suppressor protein p53; double stranded dna break; fly; drosophila melanogaster; tumor; disease control; ultraviolet rays; tumor suppressor protein; biochemistry; drosophila proteins; genes, p53; dna topoisomerases, type ii, eukaryotic; dna topoisomerase; esterases; gene regulatory networks; genes, insect; animals, genetically modified; egg proteins; oogenesis |
| Journal Title: | Science |
| Volume: | 328 |
| Issue: | 5983 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2010-06-04 |
| Start Page: | 1278 |
| End Page: | 1281 |
| Language: | English |
| DOI: | 10.1126/science.1185640 |
| PUBMED: | 20522776 |
| PROVIDER: | scopus |
| PMCID: | PMC2917750 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: SCIEA" - "Source: Scopus" |
