UV damage causes uncontrolled DNA breakage in cells from patients with combined features of XP-D and Cockayne syndrome

被引:48
作者
Berneburg, M
Lowe, JE
Nardo, T
Araújo, S
Fousteri, MI
Green, MHL
Krutmann, J
Wood, RD
Stefanini, M
Lehmann, AR [1 ]
机构
[1] Univ Sussex, MRC, Cell Mutat Unit, Brighton BN1 9RR, E Sussex, England
[2] Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England
[3] Imperial Canc Res Fund, Clare Hall Labs, S Mimms EN6 3LD, Herts, England
[4] Ist Genet Biochim & Evolutionist, CNR, Pavia, Italy
[5] Univ Dusseldorf, D-40225 Dusseldorf, Germany
关键词
Cockayne syndrome; DNA breaks; nucleotide excision repair; UV light; xeroderma pigmentosum;
D O I
10.1093/emboj/19.5.1157
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nucleotide excision repair (NER) removes damage from DNA in a tightly regulated multiprotein process. Defects in NER result in three different human disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS), Two cases with the combined features of XP and CS have been assigned to the XP-D complementation group. Despite their extreme UV sensitivity, these cells appeared to incise their DNA as efficiently as normal cells in response to UV damage. These incisions were, however, uncoupled from the rest of the repair process. Using cell-free extracts? we were unable to detect any incision activity in the neighbourhood of the damage. When irradiated plasmids were introduced into unirradiated XP-D/CS cells, the ectopically introduced damage triggered the induction of breaks in the undamaged genomic DNA, XP-D/CS cells thus have a unique response to sensing UV damage, which results in the introduction of breaks into the DNA at sites distant from the damage,We propose that it is these spurious breaks that are responsible for the extreme UV sensitivity of these cells.
引用
收藏
页码:1157 / 1166
页数:10
相关论文
共 31 条
  • [21] COCKAYNE SYNDROME - REVIEW OF 140 CASES
    NANCE, MA
    BERRY, SA
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS, 1992, 42 (01): : 68 - 84
  • [22] INITIAL RATES OF DNA INCISION IN UV-IRRADIATED HUMAN-CELLS - DIFFERENCES BETWEEN NORMAL, XERODERMA PIGMENTOSUM AND TUMOR-CELLS
    SQUIRES, S
    JOHNSON, RT
    COLLINS, ARS
    [J]. MUTATION RESEARCH, 1982, 95 (2-3): : 389 - 404
  • [23] DIFFERENT FORMS OF TFIIH FOR TRANSCRIPTION AND DNA-REPAIR - HOLO-TFIIH AND A NUCLEOTIDE EXCISION REPAIROSOME
    SVEJSTRUP, JQ
    WANG, ZG
    FEAVER, WJ
    WU, XH
    BUSHNELL, DA
    DONAHUE, TF
    FRIEDBERG, EC
    KORNBERG, RD
    [J]. CELL, 1995, 80 (01) : 21 - 28
  • [24] TAKAYAMA K, 1995, CANCER RES, V55, P5656
  • [25] Taylor EM, 1998, INT J RADIAT BIOL, V74, P277
  • [26] Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene
    Taylor, EM
    Broughton, BC
    Botta, E
    Stefanini, M
    Sarasin, A
    Jaspers, NGJ
    Fawcett, H
    Harcourt, SA
    Arlett, CF
    Lehmann, AR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (16) : 8658 - 8663
  • [27] Cells from XP-D and XP-D-CS patients exhibit equally inefficient repair of UV-induced damage in transcribed genes but different capacity to recover UV-inhibited transcription
    van Hoffen, A
    Kalle, WHJ
    de Jong-Versteeg, A
    Lehmann, AR
    van Zeeland, AA
    Mullenders, LHF
    [J]. NUCLEIC ACIDS RESEARCH, 1999, 27 (14) : 2898 - 2904
  • [28] Cockayne syndrome: defective repair of transcription?
    vanGool, AJ
    vanderHorst, G
    Citterio, E
    Hoeijmakers, JHJ
    [J]. EMBO JOURNAL, 1997, 16 (14) : 4155 - 4162
  • [29] vanOosterwijk MF, 1996, MOL CELL BIOL, V16, P4436
  • [30] DNA repair in eukaryotes
    Wood, RD
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1996, 65 : 135 - 167