This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fotiadou, P. Articles by Sweasy, J. B. Search for Related Content PubMed PubMed Citation Articles by Fotiadou, P. Articles by Sweasy, J. B.

DNA Polymerase ß Interacts with TRF2 and Induces Telomere Dysfunction in a Murine Mammary Cell Line

Departments of ¹ Therapeutic Radiology and ² Immunobiology, Yale University School of Medicine, New Haven, Connecticut

DNA polymerase ß (Polß) is a DNA repair protein that functions in base excision repair and meiosis. The enzyme has deoxyribose phosphate lyase and polymerase activity, but it is error prone because it bears no proofreading activity. Errors in DNA repair can lead to the accumulation of mutations and consequently to tumorigenesis. Polß expression has been found to be higher in tumors, and deregulation of its expression has been found to induce chromosomal instability, a hallmark of tumorigenesis, but the underlying mechanisms are unclear. In the present study, we have investigated whether ectopic expression of Polß influences the stability of chromosomes in a murine mammary cell line. The results demonstrate a telomere dysfunction phenotype: an increased rate of telomere loss and chromosome fusion, suggesting that ectopic expression of Polß leads to telomere dysfunction. In addition, Polß interacts with TRF2, a telomeric DNA binding protein. Colocalization of the two proteins occurs at nontelomeric sites and appears to be influenced by the change in the status of the telomeric complex.

This article has been cited by other articles:

				Y. Chen, Y. Yang, M. van Overbeek, J. R. Donigian, P. Baciu, T. de Lange, and M. Lei A Shared Docking Motif in TRF1 and TRF2 Used for Differential Recruitment of Telomeric Proteins Science, February 22, 2008; 319(5866): 1092 - 1096. [Abstract] [Full Text] [PDF]

				J. F. Passos, G. Saretzki, and T. von Zglinicki DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res., December 3, 2007; 35(22): 7505 - 7513. [Abstract] [Full Text] [PDF]

				L. Wang, N. Bhattacharyya, T. Rabi, L. Wang, and S. Banerjee Mammary carcinogenesis in transgenic mice expressing a dominant-negative mutant of DNA polymerase {beta} in their mammary glands Carcinogenesis, June 1, 2007; 28(6): 1356 - 1363. [Abstract] [Full Text] [PDF]

				D. C. Cabelof, Y. Ikeno, A. Nyska, R. A. Busuttil, N. Anyangwe, J. Vijg, L. H. Matherly, J. D. Tucker, S. H. Wilson, A. Richardson, et al. Haploinsufficiency in DNA Polymerase {beta} Increases Cancer Risk with Age and Alters Mortality Rate. Cancer Res., August 1, 2006; 66(15): 7460 - 7465. [Abstract] [Full Text] [PDF]

				M. Muftuoglu, H. K. Wong, S. Z. Imam, D. M. Wilson III, V. A. Bohr, and P. L. Opresko Telomere Repeat Binding Factor 2 Interacts with Base Excision Repair Proteins and Stimulates DNA Synthesis by DNA Polymerase {beta} Cancer Res., January 1, 2006; 66(1): 113 - 124. [Abstract] [Full Text] [PDF]

				L. Tomaska, S. Willcox, J. Slezakova, J. Nosek, and J. D. Griffith Taz1 Binding to a Fission Yeast Model Telomere: FORMATION OF TELOMERIC LOOPS AND HIGHER ORDER STRUCTURES J. Biol. Chem., December 3, 2004; 279(49): 50764 - 50772. [Abstract] [Full Text] [PDF]

				L. Wang, N. Bhattacharyya, D. M. Chelsea, P. F. Escobar, and S. Banerjee A Novel Nuclear Protein, MGC5306 Interacts with DNA Polymerase {beta} and Has a Potential Role in Cellular Phenotype Cancer Res., November 1, 2004; 64(21): 7673 - 7677. [Abstract] [Full Text] [PDF]