Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 16, Issue 12, Pages 1244-U59Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1725
Keywords
-
Funding
- US National Science Foundation [0602009]
- Cure Cancer Australia Foundation
- American Australian Association
- Promina postdoctoral fellowship
- Australian Postgraduate Award
- Judith Hyam Memorial Trust Fund for Cancer Research
- Cancer Council New South Wales program
- Office Of The Director
- Office Of Internatl Science &Engineering [0602009] Funding Source: National Science Foundation
Ask authors/readers for more resources
Telomere dysfunction is typically studied under conditions in which a component of the six-subunit shelterin complex that protects chromosome ends is disrupted. The nature of spontaneous telomere dysfunction is less well understood. Here we report that immortalized human cell lines lacking wild-type p53 function spontaneously show many telomeres with a DNA damage response (DDR), commonly affecting only one sister chromatid and not associated with increased chromosome end-joining. DDR+ telomeres represent an intermediate configuration between the fully capped and uncapped (fusogenic) states. In telomerase activity-positive (TA(+)) cells, DDR is associated with low TA and short telomeres. In cells using the alternative lengthening of telomeres mechanism (ALT(+)), DDR is partly independent of telomere length, mostly affects leading strand-replicated telomeres, and can be partly suppressed by TRF2 overexpression. In ALT(+) (but not TA(+)) cells, DDR+ telomeres preferentially associate with large foci of extrachromosomal telomeric DNA and recombination proteins. DDR+ telomeres therefore arise through different mechanisms in TA(+) and ALT(+) cells and have different consequences.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available