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Estrogen receptor can distinguish among various halodeoxyuridine‐substituted DNAs
Author(s) -
Kallos John,
Fasy Thomas M.,
Hollander Vincent P.,
Bick Michael D.
Publication year - 1979
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(79)80214-8
Subject(s) - medical school , library science , medicine , family medicine , medical education , computer science
Although the interplay between steroid hormone receptors and the genome has been extensively studied [l-6] , it is not yet known how the receptor protein interacts with double-stranded helical DNA. To examine the specificity and the dynamics of DNA-estrogen receptor (ER) interactions, we have initiated a study to determine how specific changes in the DNA will affect receptor binding. We have found that ER binds preferentially to AT-rich DNA [7] and also to DNA substituted with bromodeoxyuridine (BrdUrd) [8] . Numerous studies, in a wide spectrum of cell systems, have examined various changes in gene expression which follow BrdUrd-substitution in the DNA [9,10] . Relatively few experiments, however, have focused on the possible mechanism(s) by which this defined replacement (of the S-methyl group in thymine by a bromide atom) might cause subtle electronic or steric effects in DNA which, in turn, might alter gene expression in the eukaryotic cell [g-12]. One such mechanism involves altered binding of regulatory proteins to BrdUrd-substituted DNA [g-12]. One approach to the question of how the bromine atom causes its particular effects, is to ask if other halogen atoms in the same position cause the same effects [ 121. Therefore, we have incorporated 5-chloro-, 5-bromoand Siodo-deoxyuridine into DNA in equivalent molar amounts and determined the effect of these substitutions on the ER-