| Autor: |
Rebecca Cook, Georgia Zoumpoulidou, Maciej T. Luczynski, Simone Rieger, Jayne Moquet, Victoria J. Spanswick, John A. Hartley, Kai Rothkamm, Paul H. Huang, Sibylle Mittnacht |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 10, Iss 12, Pp 2006-2018 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2015.02.059 |
| Popis: |
Deficiencies in DNA double-strand break (DSB) repair lead to genetic instability, a recognized cause of cancer initiation and evolution. We report that the retinoblastoma tumor suppressor protein (RB1) is required for DNA DSB repair by canonical non-homologous end-joining (cNHEJ). Support of cNHEJ involves a mechanism independent of RB1’s cell-cycle function and depends on its amino terminal domain with which it binds to NHEJ components XRCC5 and XRCC6. Cells with engineered loss of RB family function as well as cancer-derived cells with mutational RB1 loss show substantially reduced levels of cNHEJ. RB1 variants disabled for the interaction with XRCC5 and XRCC6, including a cancer-associated variant, are unable to support cNHEJ despite being able to confer cell-cycle control. Our data identify RB1 loss as a candidate driver of structural genomic instability and a causative factor for cancer somatic heterogeneity and evolution. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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