De Rosa, Mariarosaria (2017) DNA repair during Estrogen induced transcription. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: DNA repair during Estrogen induced transcription
Creators:
CreatorsEmail
De Rosa, Mariarosariameryderosa@gmail.com
Date: May 2017
Number of Pages: 63
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Dottorato: Medicina molecolare e biotecnologie mediche
Ciclo di dottorato: 29
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricoavvedim@unina.it
Tutor:
nomeemail
Avvedimento, Vittorio EnricoUNSPECIFIED
Date: May 2017
Number of Pages: 63
Uncontrolled Keywords: Estrogen transcription DNA oxidation repair enzymes methylation
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited: 02 May 2017 13:58
Last Modified: 13 Mar 2018 11:25
URI: http://www.fedoa.unina.it/id/eprint/11695
DOI: 10.6093/UNINA/FEDOA/11695

Abstract

Estrogen-induced transcription is characterized by localized histone demethylation and DNA oxidation, followed by the recruitment of repair and DNA and histone methyl-transferase enzymes at target sites. The functional link between these different proteins recruited at estrogen chromatin sites is unclear and it is unknown which steps catalyzed by these proteins are essential for productive estrogen-mediated transcription. Here we report that specific genomic regions that synchronously recruit estrogen receptor complexed with the demethylase LSD1 and DNA repair protein such as OGG1 (a component of base excision repair) or topoisomerase IIβ. These enzymes are recruited at the estrogen regulatory regions in a precise temporal order and are essential for the assembly of the transcription initiation complex induced by estrogens. We find that DNA methyltransferase 3a (DNMT3a) couples BER and NER repair enzymes at promoter sites and stimulates estrogen-induced transcription initiation. The orderly recruitment of DNA and histone methyltransferases and repair enzymes greatly reduces the mutational burden induced by DNA oxidation associated with transcription.

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