biostudies-literature00530Oganesian LNCI NIH HHSNIGMS NIH HHS238-45https://www.ebi.ac.uk/biostudies/studies/S-EPMC3594334biostudies-literatureUnknown12(3)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.DNA repair5' C-rich telomeric overhangs are an outcome of rapid telomere truncation events.PMC3594334GM087476P30 CA014195-38P30 CA014195R01 GM087476Oganesian LKarlseder J53false5' C-rich telomeric overhangs are an outcome of rapid telomere truncation events.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.2013-01-01T00:00:00Z2013 Mar2021-02-20T18:13:10Z2019-03-27T01:05:55ZS-EPMC35943342334761610.1016/j.dnarep.2012.12.008