NDLI: Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function1

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Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function1

Content Provider	PubMed Central
Author	Jaiswal, Aruna S. Armas, Melissa L. Izumi, Tadahide Strauss, Phyllis R. Narayan, Satya
Copyright Year	2012
Abstract	In previous studies, we found that adenomatous polyposis coli (APC) blocks the base excision repair (BER) pathway by interacting with 5′-flap endonuclease 1 (Fen1). In this study, we identify the molecular features that contribute to the formation and/or stabilization of the APC/Fen1 complex that determines the extent of BER inhibition, and the subsequent accumulation of DNA damage creates mutagenic lesions leading to transformation susceptibility. We show here that APC binds to the nuclear localization sequence of Fen1 (Lys365Lys366Lys367), which prevents entry of Fen1 into the nucleus and participation in Pol-β-directed long-patch BER. We also show that levels of the APC/Fen1 complex are higher in breast tumors than in the surrounding normal tissues. These studies demonstrate a novel role for APC in the suppression of Fen1 activity in the BER pathway and a new biomarker profile to be explored to identify individuals who may be susceptible to the development of mammary and other tumors.
Starting Page	495
File Format	PDF
ISSN	14765586
e-ISSN	14765586
Journal	Neoplasia (New York, N.Y.)
Issue Number	6
Volume Number	14
Language	English
Publisher	Neoplasia Press Inc.
Publisher Date	2012-06-01
Access Restriction	Open
Rights Holder	Neoplasia Press Inc.
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research

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