Linked Life Data

8634251

Source:http://linkedlifedata.com/resource/pubmed/id/8634251

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1996-7-8
pubmed:abstractText
Ixr1 is a yeast HMG-domain protein that binds specifically to DNA adducts formed by the antitumor drug cisplatin. Interruption of the IXR1 gene in yeast desensitizes cells to cisplatin. This effect is unrelated to a natural function of Ixr1, which is to repress the transcription of COX5b. Ixr1 interacts specifically and preferentially with DNA modified by cisplatin. In the present work, Ixr1 was purified from a clone expressed in Escherichia coli. The dissociation constant for Ixr1 binding site-specifically to a 92-bp probe containing a single cis-[Pt(NH3)2{d(GpG)-N7(1) -N7(2)}] intrastrand cross-link was measured to be 2.5 (+/- 0.1) x 10(-7) M, similar to that found for HMG1. Ixr1 binds at least an order of magnitude more tightly to cisplatin-DNA adducts than to unmodified DNA. Hydroxyl radical footprinting revealed that Ixr1 protects an area of platinated DNA that is approximately 15 bp in size and centered at the platinum adduct. The binding of HMG-domain proteins to cisplatin-DNA adducts has been proposed to divert these proteins from their natural DNA-binding sites, disrupting transcription. This hypothesis was tested for Ixr1 in yeast. The protein was not titrated away from the Cox5b promoter sufficiently well to disrupt transcription either of Cox5b mRNA from genomic DNA or of the beta-galactosidase gene under control of the promoter in a plasmid DNA transformed into yeast.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6089-99
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Binding of Ixr1, a yeast HMG-domain protein, to cisplatin-DNA adducts in vitro and in vivo.
pubmed:affiliation
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.