Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function
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 de...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558612801059 |
| _version_ | 1818834728562720768 |
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| author | Aruna S. Jaiswal Melissa L. Armas Tadahide Izumi Phyllis R. Strauss Satya Narayan |
| author_facet | Aruna S. Jaiswal Melissa L. Armas Tadahide Izumi Phyllis R. Strauss Satya Narayan |
| author_sort | Aruna S. Jaiswal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T02:39:26Z |
| format | Article |
| id | doaj.art-91affa55d05f4d979a0578d0c456dfae |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-19T02:39:26Z |
| publishDate | 2012-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-91affa55d05f4d979a0578d0c456dfae2022-12-21T20:39:12ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022012-06-0114649550810.1593/neo.12680Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and FunctionAruna S. Jaiswal0Melissa L. Armas1Tadahide Izumi2Phyllis R. Strauss3Satya Narayan4Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FLDepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FLGraduate Center for Toxicology, Lexington, KYDepartment of Biology, Northeastern University, Boston, MADepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FLIn 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.http://www.sciencedirect.com/science/article/pii/S1476558612801059 |
| spellingShingle | Aruna S. Jaiswal Melissa L. Armas Tadahide Izumi Phyllis R. Strauss Satya Narayan Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function Neoplasia: An International Journal for Oncology Research |
| title | Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function |
| title_full | Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function |
| title_fullStr | Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function |
| title_full_unstemmed | Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function |
| title_short | Adenomatous Polyposis Coli Interacts with Flap Endonuclease 1 to Block Its Nuclear Entry and Function |
| title_sort | adenomatous polyposis coli interacts with flap endonuclease 1 to block its nuclear entry and function |
| url | http://www.sciencedirect.com/science/article/pii/S1476558612801059 |
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