論文 - 詳細
| RRC ID | 72867 |
|---|---|
| 著者 | Arun Prakash Mishra, Suzanne A. Hartford, Sounak Sahu, Kimberly Klarmann, Rajani Kant Chittela, Kajal Biswas, Albert B. Jeon, Betty K. Martin, Sandra Burkett, Eileen Southon, Susan Reid, Mary E. Albaugh, Baktiar Karim, Lino Tessarollo, Jonathan R. Keller, Shyam K. Sharan |
| タイトル | BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks |
| ジャーナル | Nature Communications |
| Abstract |
The interaction between tumor suppressor BRCA2 and DSS1 is essential for RAD51 recruitment and repair of DNA double stand breaks (DSBs) by homologous recombination (HR). We have generated mice with a leucine to proline substitution at position 2431 of BRCA2, which disrupts this interaction. Although a significant number of mutant mice die during embryogenesis, some homozygous and hemizygous mutant mice undergo normal postnatal development. Despite lack of radiation induced RAD51 foci formation and a severe HR defect in somatic cells, mutant mice are fertile and exhibit normal RAD51 recruitment during meiosis. We hypothesize that the presence of homologous chromosomes in close proximity during early prophase I may compensate for the defect in BRCA2-DSS1 interaction. We show the restoration of RAD51 foci in mutant cells when Topoisomerase I inhibitor-induced single strand breaks are converted into DSBs during DNA replication. We also partially rescue the HR defect by tethering the donor DNA to the site of DSBs using streptavidin-fused Cas9. Our findings demonstrate that the BRCA2-DSS1 complex is dispensable for RAD51 loading when the homologous DNA is close to the DSB. |
| 巻・号 | 13 |
| 公開日 | 2022-12-1 |
| DOI | 10.1038/s41467-022-29409-y |
| PMID | 35365640 |
| PMC | PMC8975877 |
| MeSH | Animals DNA DNA Breaks, Double-Stranded* DNA Repair / genetics Homologous Recombination Mice Rad51 Recombinase* / genetics Rad51 Recombinase* / metabolism |
| IF | 12.121 |
| リソース情報 | |
| 実験動物マウス | RBRC10583 |