title: Interaction of estrogen receptor alpha with 3-methyladenine DNA glycosylase modulates transcription and DNA repair.
abstract: Estrogen receptor alpha (ERalpha) interacts with basal transcription factors, coregulatory proteins, and chromatin modifiers to initiate transcription of the target genes. We have identified a novel interaction between ERalpha and the DNA repair protein 3-methyladenine DNA glycosylase (MPG) thereby providing a functional link between gene expression and DNA repair. Interestingly, the ERalpha-MPG interaction was enhanced by the presence of estrogen response element (ERE)-containing DNA. In vitro pull-down assays indicated that the interaction of ERalpha with MPG was direct and occurred through the DNA- and ligand-binding domains and the hinge region of the receptor. More importantly, endogenously expressed ERalpha and MPG from MCF-7 cells coimmunoprecipitated with ERalpha- and MPG-specific antibodies. The ERalpha-MPG interaction had functional consequences on the activities of both proteins. ERalpha increased MPG acetylation, stabilized the binding of MPG with hypoxanthine-containing oligos, and enhanced MPG-catalyzed removal of hypoxanthine from DNA. In turn, MPG dramatically stabilized the interaction of ERalpha with ERE-containing oligos, decreased p300-mediated acetylation of the receptor, and reduced transcription of simple and complex ERE-containing reporter plasmids in a dose-dependent manner. Our studies suggest that recruitment of MPG to ERE-containing genes influences transcription and plays a role in maintaining integrity of the genome by recruiting DNA repair proteins to actively transcribing DNA.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: Varsha S
authors.initials: VS
authors.lastname: Likhite
authors.forename: Emily I
authors.initials: EI
authors.lastname: Cass
authors.forename: Scott D
authors.initials: SD
authors.lastname: Anderson
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Ann M
authors.initials: AM
authors.lastname: Nardulli
mesh_terms: D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D047628:Estrogen Receptor alpha; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases