Fanconi anemia complementation group FANCD2 protein serine 331 phosphorylation is important for fanconi anemia pathway function and BRCA2 interaction.

Fanconi anemia is a cancer-prone inherited bone marrow failure and cancer susceptibility syndrome with at least 13 complementation groups (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, and FANCN). Our laboratory has previously described several regulatory phosphorylation events for core complex member proteins FANCG and FANCA ...
by phosphorylation. In this study, we report a novel phosphorylation site serine 331 (S331) of FANCD2, the pivotal downstream player of the Fanconi anemia pathway. Phosphorylation of S331 is important for its DNA damage-inducible monoubiquitylation, resistance to DNA cross-linkers, and in vivo interaction with FANCD1/BRCA2. A phosphomimetic mutation at S331 restores all of these phenotypes to wild-type. In vitro and in vivo experiments show that phosphorylation of S331 is mediated by CHK1, the S-phase checkpoint kinase implicated in the Fanconi anemia DNA repair pathway.
Mesh Terms:
Amino Acid Sequence, Animals, BRCA2 Protein, Cell Line, DNA Damage, Fanconi Anemia, Fanconi Anemia Complementation Group D2 Protein, Fanconi Anemia Complementation Group Proteins, Humans, Immunoblotting, Immunoprecipitation, Mass Spectrometry, Phosphorylation, Protein Kinases, Sequence Homology, Amino Acid, Serine, Signal Transduction
Cancer Res.
Date: Nov. 15, 2009
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