Induction of apoptosis by telomere 3′ overhang-specific DNA

被引:69
作者
Eller, MS [1 ]
Puri, N [1 ]
Hadshiew, IM [1 ]
Venna, SS [1 ]
Gilchrest, BA [1 ]
机构
[1] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA
关键词
DNA damage; apoptosis; telomeres; p53; p73; E2F1;
D O I
10.1006/excr.2002.5531
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Telomeres are tandem repeats of a specific TTAGGG nucleotide sequence at the ends of chromosomes. Telomere shortening is proposed to act as a biological clock and cancer prevention mechanism by inducing a nonproliferative, senescent phenotype after a limited number of cellular divisions. Recent evidence also suggests that telomere disruption can trigger apoptosis in certain cell types, mimicking a major cellular response to DNA damage. Here, we show that addition of DNA oligonucleotides homologous to the telomere 3' overhang sequence causes lymphocytic (Jurkat) cells to undergo apoptosis, as described for lymphocytes following telomere loop disruption. We further implicate the p53 tumor suppressor and transcription factor, as well as the p53 homolog p73 and the E2F1 transcription factor, in mediating the apoptotic response. We propose that exposure of the telomere 3' overhang due to opening of the normal telomere loop structure is a physiologic signal for these DNA damage-like responses in vivo and that oligonucleotides partially or completely homologous to the telomere overhang mimic this signal in the absence of DNA damage or telomere disruption. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:185 / 193
页数:9
相关论文
共 49 条
  • [11] Recovery of the normal p53 response after UV treatment in DNA repair-deficient fibroblasts by retroviral-mediated correction with the XPD gene
    Dumaz, N
    Drougard, C
    Quilliet, X
    Mezzina, M
    Sarasin, A
    Daya-Grosjean, L
    [J]. CARCINOGENESIS, 1998, 19 (09) : 1701 - 1704
  • [12] DNA-DAMAGE AND MELANOGENESIS
    ELLER, MS
    YAAR, M
    GILCHREST, BA
    [J]. NATURE, 1994, 372 (6505) : 413 - 414
  • [13] DNA damage enhances melanogenesis
    Eller, MS
    Ostrom, K
    Gilchrest, BA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (03) : 1087 - 1092
  • [14] Enhancement of DNA repair in human skin cells by thymidine dinucleotides: Evidence for a p53-mediated mammalian SOS response
    Eller, MS
    Maeda, T
    Magnoni, C
    Atwal, D
    Gilchrest, BA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (23) : 12627 - 12632
  • [15] THE RNA COMPONENT OF HUMAN TELOMERASE
    FENG, JL
    FUNK, WD
    WANG, SS
    WEINRICH, SL
    AVILION, AA
    CHIU, CP
    ADAMS, RR
    CHANG, E
    ALLSOPP, RC
    YU, JH
    LE, SY
    WEST, MD
    HARLEY, CB
    ANDREWS, WH
    GREIDER, CW
    VILLEPONTEAU, B
    [J]. SCIENCE, 1995, 269 (5228) : 1236 - 1241
  • [16] FRIEDBERG EC, 1995, DNA REPAIR MUTAGENES, P1
  • [17] ATM-dependent phosphorylation of nibrin in response to radiation exposure
    Gatei, M
    Young, D
    Cerosaletti, KM
    Desai-Mehta, A
    Spring, K
    Kozlov, S
    Lavin, MF
    Gatti, RA
    Concannon, P
    Khanna, K
    [J]. NATURE GENETICS, 2000, 25 (01) : 115 - 119
  • [18] Thymidine dinucleotide mimics the effect of solar simulated irradiation on p53 and p53-regulated proteins
    Goukassian, DA
    Eller, MS
    Yaar, M
    Gilchrest, BA
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1999, 112 (01) : 25 - 31
  • [19] GOUKASSIAN DA, 2002, FASEB J
  • [20] Telomere length regulation
    Greider, CW
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1996, 65 : 337 - 365