Journal
GENES & DEVELOPMENT
Volume 23, Issue 5, Pages 555-560Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1761309
Keywords
Fanconi anemia; FANCM; mitosis; beta-TRCP; Plk1; ubiquitin
Categories
Funding
- NIH [RO1-HL52725, RO1-DK43889, PO1-HL54785]
- Leukemia and Lymphoma Society Fellowship
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The 13 Fanconi anemia (FA) proteins cooperate in a common DNA repair pathway. Eight of these proteins are assembled into a multisubunit E3 ligase called the FA core complex. During S phase, the FA core complex is loaded by the FANCM protein into chromatin where it monoubiquitinates its substrates. In mitosis, the FA core complex is released from FANCM by an unknown mechanism. Here we show that FANCM is hyper-phosphorylated and degraded during mitosis. beta-TRCP and Plk1 are the key regulators of FANCM degradation. Nondegradable mutant forms of FANCM retain the FA core complex in the chromatin and disrupt the FA pathway. Our data provide a novel mechanism for the cell cycle-dependent regulation of the FA pathway.
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