Phosphorylation of H2AX at short telomeres in T cells and fibroblasts.
Eukaryotic cells undergo arrest and enter apoptosis in response to short telomeres. T cells from late generation mTR(-/-) mice that lack telomerase show increased apoptosis when stimulated to enter the cell cycle. The increased apoptosis was not inhibited by colcemid, indicating that the response did not result from breakage of dicentric chromosomes at mitosis. The damage response protein gamma-H2AX localized to telomeres in metaphases from T cells and fibroblasts from mTR(-/-) cells with short telomeres. These data suggest that the major mechanism for induction of apoptosis in late generation mTR(-/-) cells is independent of chromosome segregation and that loss of telomere function through progressive telomere shortening in the absence of telomerase leads to recognition of telomeres as DNA breaks.
Graduate Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Ling-Yang
LY
Hao
Margaret A
MA
Strong
Carol W
CW
Greider
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D002469:Cell Separation; D002875:Chromosomes / Q000648:ultrastructure; D004396:Coloring Agents / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D007621:Karyotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008934:Mitogens / Q000737:chemistry; D008938:Mitosis; D010766:Phosphorylation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016615:Telomere / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors; D019076:Transgenes
D017304:Annexin A5; D004396:Coloring Agents; C468783:H2AX protein, human; D006657:Histones; D008934:Mitogens; C475961:gamma-H2AX protein, mouse; D004247:DNA; D001973:Bromodeoxyuridine