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Fanconi anemia is characterized (among other things) by an increased tumor incidence and cellular sensitivity to DNA damaging agents. The FANCD2 protein is thought to be a target of ATM/ATR DNA-damage sensing kinases, and specifically to be involved in the repair of intrastrand crosslinks. Defects in FANCD2 leads to a failure of the radiation-induced block to DNA replication.

fancD2 is roughly threefold overexpressed in growth-phase cells of a Dicty strain in which the retinoblastoma-like gene rblA has been inactivated. Most genes associated with cell cycle progression are overexpressed in this strain. Unlike many such genes, however, fncD2 overexpression is confined to the growth phase. The protein has a mitotic destruction box, and is one of 336 known proteins in which this motif is present in both D discoideum and D purpureum. The context of the element is only weakly conserved, thus the conservation of the R, L and N residues in RxxLxxxxN is particularly suggestive.

TVKSIRNGLKFSSNNKNTSN   D purpureum
TGVVFRYLLEHLKNLSNQFK   D discoideum

All in all it seems likely that this protein plays a role in normal cell cycle progression.

Harry MacWilliams, August 2009

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