BINDING OF TRANSCRIPTION FACTORS CREATES HOT-SPOTS FOR UV PHOTOPRODUCTS INVIVO

被引:133
作者
PFEIFER, GP
DROUIN, R
RIGGS, AD
HOLMQUIST, GP
机构
[1] Department of Biology, Beckman Res. Inst. City of Hope, Duarte
关键词
D O I
10.1128/MCB.12.4.1798
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
Cyclobutane dipyrimidines and <6-4> dipyrimidines are the two major classes of mutagenic DNA photoproducts produced by UV irradiation of cells. We developed a method to map cyclobutane dipyrimidines at the DNA sequence level in mammalian cells. The frequency of this class of photoproducts was determined at every dipyrimidine along the human phosphoglycerate kinase-1 (PGK1) promoter sequence and was compared to the UV-induced frequency distribution of <6-4> dipyrimidines. After irradiation of living cells containing active or inactive PGK1 genes, enzymatic or chemical cleavage at UV photoproducts, and amplification by ligation-mediated polymerase chain reaction, photofootprints were seen in all regions which bind transcription factors and appear as DNase I footprints. Photoproduct frequency within transcription factor binding sites was suppressed or enhanced relative to inactive genes or naked DNA with enhancements of up to 30-fold. Since photoproducts are mutagenic, this indicates that photoproduct (mutation?) hot spots may be tissue specific in mammals.
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页码:1798 / 1804
页数:7
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