Premium
Spreading of mammalian DNA‐damage response factors studied by ChIP‐chip at damaged telomeres
Author(s) -
Meier Andreas,
Fiegler Heike,
Muñoz Purificacion,
Ellis Peter,
Rigler Diane,
Langford Cordelia,
Blasco Maria A,
Carter Nigel,
Jackson Stephen P
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601719
Subject(s) - biology , telomere , dna damage , chip , dna , genetics , microbiology and biotechnology , electrical engineering , engineering
Phosphorylated histone H2AX (γH2AX) is generated in nucleosomes flanking sites of DNA double‐strand breaks, triggering the recruitment of DNA‐damage response proteins such as MDC1 and 53BP1. Here, we study shortened telomeres in senescent human cells. We show that most telomeres trigger γH2AX formation, which spreads up to 570 kb into the subtelomeric regions. Furthermore, we reveal that the spreading patterns of 53BP1 and MDC1 are very similar to that of γH2AX, consistent with a structural link between these factors. Moreover, different subsets of telomeres signal in different cell lines, with those that signal tending to equate to the shortest telomeres of the corresponding cell line, thus linking telomere attrition with DNA‐damage signalling. Notably, we find that, in some cases, γH2AX spreading is modulated in a manner suggesting that H2AX distribution or its ability to be phosphorylated is not uniform along the chromosome. Finally, we observe weak γH2AX signals at telomeres of proliferating cells, but not in hTERT immortalised cells, suggesting that low telomerase activity leads to telomere uncapping and senescence in proliferating primary cells.