title: The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells.
abstract: Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells.
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, PO BOX 1495, Spokane, WA 99210, United States.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, PO BOX 1495, Spokane, WA 99210, United States.
authors.forename: Pingping
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, PO BOX 1495, Spokane, WA 99210, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Chastain
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, PO BOX 1495, Spokane, WA 99210, United States.
authors.forename: Olga
authors.initials: O
authors.lastname: Shiva
authors.affiliation: Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, PO BOX 1495, Spokane, WA 99210, United States. Electronic address: wchai@wsu.edu.
authors.forename: Weihang
authors.initials: W
authors.lastname: Chai
mesh_terms: D049109:Cell Proliferation; D006801:Humans; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C544945:Ctc1 protein, human; C544946:Stn1 protein, human; D034501:Telomere-Binding Proteins; C544947:Ten1 protein, human
keywords: ALT; CTC1/STN1/TEN1; Telomere