کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1980246 | 1061834 | 2013 | 8 صفحه PDF | دانلود رایگان |
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.
► A DNA damage signal is not required for the formation of 5′ C-rich overhangs at the chromosome end.
► 5′ C-overhangs do not necessarily trigger a DNA damage response.
► 5′ C-overhangs are an outcome of telomere truncation events, which give rise to circular extra-chromosomal telomeric repeats.
► De novo formation of telomeric C-overhangs is partly XRCC3 dependent.
Journal: DNA Repair - Volume 12, Issue 3, 1 March 2013, Pages 238–245