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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. - Highlights: • CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle. • CST is important for promoting telomeric DNA replication in ALT cells. • CST deficiency decreases ECTR formation and increases T-SCE. • CST deficiency impairs ALT cellmore » proliferation and results in multinucleation.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22649859
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 355; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABUNDANCE; AMPLIFICATION; CARBON; CARBON MONOXIDE; CELL CYCLE; CELL PROLIFERATION; CHROMATIDS; CHROMOSOMES; COMPLEXES; DNA; DNA REPLICATION; ELECTROPHORESIS; FLUORESCENCE; GELS; INHIBITION; IN-SITU HYBRIDIZATION; INSTABILITY; LEUKEMIA; RECOMBINATION; SISTER CHROMATID EXCHANGES; TELOMERES

Citation Formats

Huang, Chenhui, Jia, Pingping, Chastain, Megan, Shiva, Olga, and Chai, Weihang, E-mail: wchai@wsu.edu. The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.03.058.
Huang, Chenhui, Jia, Pingping, Chastain, Megan, Shiva, Olga, & Chai, Weihang, E-mail: wchai@wsu.edu. The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells. United States. doi:10.1016/J.YEXCR.2017.03.058.
Huang, Chenhui, Jia, Pingping, Chastain, Megan, Shiva, Olga, and Chai, Weihang, E-mail: wchai@wsu.edu. Thu . "The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells". United States. doi:10.1016/J.YEXCR.2017.03.058.
@article{osti_22649859,
title = {The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells},
author = {Huang, Chenhui and Jia, Pingping and Chastain, Megan and Shiva, Olga and Chai, Weihang, E-mail: wchai@wsu.edu},
abstractNote = {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. - Highlights: • CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle. • CST is important for promoting telomeric DNA replication in ALT cells. • CST deficiency decreases ECTR formation and increases T-SCE. • CST deficiency impairs ALT cell proliferation and results in multinucleation.},
doi = {10.1016/J.YEXCR.2017.03.058},
journal = {Experimental Cell Research},
number = 2,
volume = 355,
place = {United States},
year = {Thu Jun 15 00:00:00 EDT 2017},
month = {Thu Jun 15 00:00:00 EDT 2017}
}