Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/26839
Title: The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of Telomeres
Authors: Mendez-Bermudez, A.
Hidalgo-Bravo, A.
Cotton, V. E.
Gravani, A.
Jeyapalan, J. N.
Royle, N. J.
First Published: 18-Sep-2012
Publisher: Oxford University Press
Citation: Nucleic Acids Research, 2012, 40(21), pp. 10809–10820
Abstract: Approximately 10% of all cancers, but a higher proportion of sarcomas, use the recombination-based alternative lengthening of telomeres (ALT) to maintain telomeres. Two RecQ helicase genes, BLM and WRN, play important roles in homologous recombination repair and they have been implicated in telomeric recombination activity, but their precise roles in ALT are unclear. Using analysis of sequence variation present in human telomeres, we found that a WRN- ALT+ cell line lacks the class of complex telomere mutations attributed to inter-telomeric recombination in other ALT+ cell lines. This suggests that WRN facilitates inter-telomeric recombination when there are sequence differences between the donor and recipient molecules or that sister-telomere interactions are suppressed in the presence of WRN and this promotes inter-telomeric recombination. Depleting BLM in the WRN- ALT+ cell line increased the mutation frequency at telomeres and at the MS32 minisatellite, which is a marker of ALT. The absence of complex telomere mutations persisted in BLM-depleted clones, and there was a clear increase in sequence homogenization across the telomere and MS32 repeat arrays. These data indicate that BLM suppresses unequal sister chromatid interactions that result in excessive homogenization at MS32 and at telomeres in ALT+ cells.
DOI Link: 10.1093/nar/gks862
ISSN: 0305-1048
eISSN: 1362-4962
Links: http://hdl.handle.net/2381/26839
http://nar.oxfordjournals.org/content/40/21/10809
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © The Author(s) 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted, distribution, and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Genetics

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