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DNA Repair (Amst). 2013 Mar 1;12(3):238-45. doi: 10.1016/j.dnarep.2012.12.008. Epub 2013 Jan 21.

5' C-rich telomeric overhangs are an outcome of rapid telomere truncation events.

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The Salk Institute for Biological Studies, Molecular and Cellular Biology Department, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.


A subset of human tumors ensures indefinite telomere length maintenance by activating a telomerase-independent mechanism known as Alternative Lengthening of Telomeres (ALT). Most tumor cells of ALT origin share a constellation of unique characteristics, which include large stores of extra-chromosomal telomeric material, chronic telomere dysfunction and a peculiar enrichment in chromosome ends with 5' C-rich overhangs. Here we demonstrate that acute telomere de-protection and the subsequent DNA damage signal are not sufficient to facilitate formation of 5' C-overhangs at the chromosome end. Rather chromosome ends bearing 5' C-overhangs are a by-product of rapid cleavage events, processing of which occurs independently of the DNA damage response and is partly mediated through the XRCC3 endonuclease.

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