5' 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.
The Salk Institute for Biological Studies, Molecular and Cellular Biology Department, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Liana
L
Oganesian
Jan
J
Karlseder
D001482:Base Composition; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D059505:Telomere Homeostasis; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014898:Werner Syndrome / Q000378:metabolism
D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; C110901:X-ray repair cross complementing protein 3