Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway.

Article Details

Citation

Wang X, Kennedy RD, Ray K, Stuckert P, Ellenberger T, D'Andrea AD

Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway.

Mol Cell Biol. 2007 Apr;27(8):3098-108. Epub 2007 Feb 12.

PubMed ID
17296736 [ View in PubMed
]
Abstract

The eleven Fanconi anemia (FA) proteins cooperate in a novel pathway required for the repair of DNA cross-links. Eight of the FA proteins (A, B, C, E, F, G, L, and M) form a core enzyme complex, required for the monoubiquitination of FANCD2 and the assembly of FANCD2 nuclear foci. Here, we show that, in response to DNA damage, Chk1 directly phosphorylates the FANCE subunit of the FA core complex on two conserved sites (threonine 346 and serine 374). Phosphorylated FANCE assembles in nuclear foci and colocalizes with FANCD2. A nonphosphorylated mutant form of FANCE (FANCE-T346A/S374A), when expressed in a FANCE-deficient cell line, allows FANCD2 monoubiquitination, FANCD2 foci assembly, and normal S-phase progression. However, the mutant FANCE protein fails to complement the mitomycin C hypersensitivity of the transfected cells. Taken together, these results elucidate a novel role of Chk1 in the regulation of the FA/BRCA pathway and in DNA cross-link repair. Chk1-mediated phosphorylation of FANCE is required for a function independent of FANCD2 monoubiquitination.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Serine/threonine-protein kinase Chk1O14757Details