Hindawi Publishing Corporation Journal of Oncology Volume 2012, Article ID 806382, 11 pages doi:10.1155/2012/806382 Research Article Modulation of Telomeres in Alternative Lengthening of Telomeres Type I Like Human Cells by the Expression of Werner Protein and Telomerase Aisha Siddiqa, 1 David Cavazos, 2 Jeffery Chavez, 1 Linda Long, 1 and Robert A. Marciniak 1, 3, 4 1 Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA 2 Department of Nutritional Sciences, School of Human Ecology, The University of Texas at Austin, Austin, TX 78712, USA 3 Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA 4 South Texas Veterans Healthcare Administration, San Antonio, TX 78229, USA Correspondence should be addressed to Robert A. Marciniak, marciniak@uthscsa.edu Received 21 October 2011; Revised 13 December 2011; Accepted 10 January 2012 Academic Editor: Frederick E. Domann Copyright © 2012 Aisha Siddiqa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The alternative lengthening of telomeres (ALT) is a recombination-based mechanism of telomere maintenance activated in 5–20% of human cancers. In Saccharomyces cerevisiae, survivors that arise after inactivation of telomerase can be classified as type I or type II ALT. In type I, telomeres have a tandem array structure, with each subunit consisting of a subtelomeric Y ′ element and short telomere sequence. Telomeres in type II have only long telomere repeats and require Sgs1, the S. cerevisiae RecQ family helicase. We previously described the first human ALT cell line, AG11395, that has a telomere structure similar to type I ALT yeast cells. This cell line lacks the activity of the Werner syndrome protein, a human RecQ helicase. The telomeres in this cell line consist of tandem repeats containing SV40 DNA, including the origin of replication, and telomere sequence. We investigated the role of the SV40 origin of replication and the effects of Werner protein and telomerase on telomere structure and maintenance in AG11395 cells. We report that the expression of Werner protein facilitates the transition in human cells of ALT type I like telomeres to type II like telomeres in some aspects. These findings have implications for the diagnosis and treatment of cancer. 1. Introduction As progressive loss of telomere DNA is associated with senes- cence [1], maintenance of telomere function is essential for indefinite cell proliferation. Most cancer cells rely on expres- sion of telomerase for suppression of telomere shortening [2]. However 5%–20% percent of cancers maintain telomeres by the alternative lengthening of telomere (ALT), a recom- bination-based mechanism [3]. Telomere maintenance mechanisms are a potential prog- nostic indicator [3] and promising target in cancer diagnosis and therapy [4–6]. Increasing evidence supports that Werner protein (WRN), a RecQ helicase and exonuclease, plays a direct role in telomere maintenance [7] and promotion of tumor cell growth [8]. WRN epigenetic silencing in human cancers leads to hypersensitivity to treatment with a number of chemotherapeutic drugs [9]. Germline mutations in the WRN gene cause an autosomal recessive disorder, Werner syndrome (WS). WS is characterized by symptoms suggestive of premature aging and by the development of mesenchymal neoplasms [10]. Strikingly, the ALT mechanism is more pre- valent in tumors arising from tissues of mesenchymal origin, such as osteosarcomas, than in those of epithelial origin [11]. It has been suggested that the telomere-telomere recombina- tion in WRN-deficient, telomere dysfunctional cells pro- motes escape from senescence and engagement of the ALT pathway [12]. Werner protein also colocalizes with telomeres in human ALT cells [13]. S. cerevisiae cells that lack functional telomerase undergo telomere attrition and lose viability [14]. Rare cells escape senescence and two types of survivors arise. Type I ALT survivors have telomeres that have a tandem array structure. The repeat unit in the array consists of a subtelomeric Y ′ element containing an ARS (yeast origin of replication)