Knockdown of mu-calpain in Fanconi anemia, FA-A, cells by siRNA restores alphaII spectrin levels and corrects chromosomal instability and defective DNA interstrand cross-link repair.

ABSTRACT: We have previously shown that there is a deficiency in the structural protein, nonerythroid alpha spectrin (alphaIISp), in cells from patients with Fanconi anemia (FA). These studies indicate that this deficiency is due to the reduced stability of alphaIISp and correlates with a decreased level of repair of DNA interstrand cross-links and chromosomal instability in FA cells. An important factor in the stability of alphaIISp is its susceptibility to cleavage by the protease, mu-calpain. We hypothesized that an increased level of mu-calpain cleavage of alphaIISp in FA cells leads to an increased level of breakdown of alphaIISp and that knocking down expression of mu-calpain in FA cells should restore levels of alphaIISp and correct a number of the phenotypic defects observed. The results sho

SUBMITTER: Zhang P 

PROVIDER: S-EPMC2899890 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature