CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair.
In: Nature, Jg. 434 (2005-03-31), Heft 7033, S. 598-604
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Zugriff:
Inherited mutations in BRCA2 are associated with a predisposition to early-onset breast cancers. The underlying basis of tumorigenesis is thought to be linked to defects in DNA double-strand break repair by homologous recombination. Here we show that the carboxy-terminal region of BRCA2, which interacts directly with the essential recombination protein RAD51, contains a site (serine?3291; S3291) that is phosphorylated by cyclin-dependent kinases. Phosphorylation of S3291 is low in S phase when recombination is active, but increases as cells progress towards mitosis. This modification blocks C-terminal interactions between BRCA2 and RAD51. However, DNA damage overcomes cell cycle regulation by decreasing S3291 phosphorylation and stimulating interactions with RAD51. These results indicate that S3291 phosphorylation might provide a molecular switch to regulate RAD51 recombination activity, providing new insight into why BRCA2 C-terminal deletions lead to radiation sensitivity and cancer predisposition. [ABSTRACT FROM AUTHOR]
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Titel: |
CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair.
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Autor/in / Beteiligte Person: | Esashi, Fumiko ; Christ, Nicole ; Gannon, Julian ; Liu, Yilun ; Hunt, Tim ; Jasin, Maria ; West, Stephen C. |
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Zeitschrift: | Nature, Jg. 434 (2005-03-31), Heft 7033, S. 598-604 |
Veröffentlichung: | 2005 |
Medientyp: | academicJournal |
ISSN: | 0028-0836 (print) |
DOI: | 10.1038/nature03404 |
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