PREFERENTIAL REPAIR OF ULTRAVIOLET LIGHT-INDUCED DNA-DAMAGE IN THE TRANSCRIBED STRAND OF THE HUMAN P53 GENE

被引:35
作者
FORD, JM [1 ]
LOMMEL, L [1 ]
HANAWALT, PC [1 ]
机构
[1] STANFORD UNIV,DEPT BIOL SCI,STANFORD,CA 94305
关键词
TRANSCRIPTION-COUPLED DNA REPAIR; TUMOR SUPPRESSOR GENE; MUTATION;
D O I
10.1002/mc.2940100208
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
Mutations in the p53 tumor suppressor gene have been found in most human tumors. Analyses of the spectrum of p53 mutations in certain tumor types have shown a bias for mutations originating from lesions presumed to be in the untranscribed strand of the gene. This implies strand specificity for the formation or repair of DNA damage. We measured the induction and repair of ultraviolet light-induced cyclobutane pyrimidine dimers (CPD) in each strand of the human p53 gene in a normal human lung fibroblast cell line using quantitative Southern hybridization. We found that the removal of CPD from the transcribed strand was more rapid than that from the untranscribed strand of this gene, although the frequency of CPD induction was similar in both strands. Preferential repair of the transcribed strand of the p53 gene may account for the mutational spectra of this gene in human tumors. (C) 1994 Wiley-Liss, Inc.
引用
收藏
页码:105 / 109
页数:5
相关论文
共 26 条
[1]   DNA-REPAIR IN AN ACTIVE GENE - REMOVAL OF PYRIMIDINE DIMERS FROM THE DHFR GENE OF CHO CELLS IS MUCH MORE EFFICIENT THAN IN THE GENOME OVERALL [J].
BOHR, VA ;
SMITH, CA ;
OKUMOTO, DS ;
HANAWALT, PC .
CELL, 1985, 40 (02) :359-369
[2]   A ROLE FOR SUNLIGHT IN SKIN-CANCER - UV-INDUCED P53 MUTATIONS IN SQUAMOUS-CELL CARCINOMA [J].
BRASH, DE ;
RUDOLPH, JA ;
SIMON, JA ;
LIN, A ;
MCKENNA, GJ ;
BADEN, HP ;
HALPERIN, AJ ;
PONTEN, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (22) :10124-10128
[3]  
CALABRETTA B, 1986, CANCER RES, V46, P5738
[4]   PREFERENTIAL REPAIR AND STRAND-SPECIFIC REPAIR OF BENZO[A]PYRENE DIOL EPOXIDE ADDUCTS IN THE HPRT GENE OF DIPLOID HUMAN FIBROBLASTS [J].
CHEN, RH ;
MAHER, VM ;
BROUWER, J ;
VANDEPUTTE, P ;
MCCORMICK, JJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5413-5417
[5]  
COLES C, 1992, CANCER RES, V52, P5291
[6]   SPECIFIC UV-INDUCED MUTATION SPECTRUM IN THE P53 GENE OF SKIN TUMORS FROM DNA-REPAIR-DEFICIENT XERODERMA-PIGMENTOSUM PATIENTS [J].
DUMAZ, N ;
DROUGARD, C ;
SARASIN, A ;
DAYAGROSJEAN, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) :10529-10533
[7]  
EVANS MK, 1993, CANCER RES, V53, P5377
[8]  
HANAWALT PC, 1992, P A BENZON S, V5, P231
[9]   DEFECTS IN A CELL-CYCLE CHECKPOINT MAY BE RESPONSIBLE FOR THE GENOMIC INSTABILITY OF CANCER-CELLS [J].
HARTWELL, L .
CELL, 1992, 71 (04) :543-546
[10]   P53 MUTATIONS IN HUMAN CANCERS [J].
HOLLSTEIN, M ;
SIDRANSKY, D ;
VOGELSTEIN, B ;
HARRIS, CC .
SCIENCE, 1991, 253 (5015) :49-53