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Adenomatous polyposis coli (APC) plays a diverse role in cellular mechanisms such as cell migration, cell adhesion, cell communication, beta-catenin regulation, chromosomal stability, cell cycle control and apoptosis. In these examples, the importance of the mutations of APC gene has been implicated. In our studies, we have shown that the APC gene is inducible in response to DNA damage and plays a role in DNA repair. We have shown that APC interacts with DNA polymerase beta (pol-beta) and blocks pol-beta-mediated strand-displacement synthesis of base excision repair (BER) (Narayan, S., Jaiswal, A. S., Balusu, R., J. Biol. Chem. 280: 6942-6949, 2005). In the present study, we have characterized the BER interaction region of APC and named it DNA repair inhibitory (DRI)-domain, in which amino acid I1259 and Y1262 are critical for interaction. In most cases, the DRI-domain of APC is spared by mutator cluster region, suggesting that both the wild-type and mutant APC can play a role in BER. We further examined that flap endonuclease-1 (Fen-1) interacts with APC at the DRI-domain. Our functional assays showed that APC blocks Fen-1 cleavage activity and thus play a role in strand-displacement synthesis. These studies are novel and will have future implications in DNA damage-induced chemoprevention and carcinogenesis.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]