Gutenberg Open Science: Widespread transcriptional gene inactivation initiated by a repair intermediate of 8-oxoguanine

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7999

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DC Field	Value	Language
dc.contributor.author	Allgayer, Julia	-
dc.contributor.author	Kitsera, Nataliya	-
dc.contributor.author	Bartelt, Solveig	-
dc.contributor.author	Epe, Bernd	-
dc.contributor.author	Khobta, Andriy	-
dc.date.accessioned	2022-10-14T07:17:22Z	-
dc.date.available	2022-10-14T07:17:22Z	-
dc.date.issued	2016
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8014	-
dc.description.abstract	DNA damage can significantly modulate expression of the affected genes either by direct structural interference with transcription components or as a collateral outcome of cellular repair attempts. Thus, DNA glycosylases of the base excision repair (BER) pathway have been implicated in negative transcriptional response to several spontaneously generated DNA base modifications, including a common oxidative DNA base modification 8-oxoguanine (8-oxoG). Here, we report that single 8-oxoG situated in the non-transcribed DNA strand of a reporter gene has a pronounced negative effect on transcription, driven by promoters of various strength and with different structural properties, including viral, human, and artificial promoters. We further show that the magnitude of the negative effect on the gene expression correlates with excision of the modified base by OGG1 in all promoter constructs tested. Moreover, by using expression vectors with nuclease resistant backbone modifications, we demonstrate that OGG1 does not catalyse DNA strand cleavage in vivo. Rather, cleavage of the phosphate bond 5′ to 8-oxodG (catalysed by APE1) is essential and universally required for the onset of transcriptional silencing, regardless of the promoter structure. Hence, induction of transcriptional silencing emerges as a ubiquitous mode of biological response to 8-oxoG in DNA.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY-NC	*
dc.rights.uri	https://creativecommons.org/licenses/by-nc/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Widespread transcriptional gene inactivation initiated by a repair intermediate of 8-oxoguanine	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7999	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 09 Chemie, Pharmazie u. Geowissensch.	de
jgu.organisation.number	7950	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Nucleic acids research	de
jgu.journal.volume	44	de
jgu.journal.issue	15	de
jgu.pages.start	7267	de
jgu.pages.end	7280	de
jgu.publisher.year	2016	-
jgu.publisher.name	Oxford Univ. Press	de
jgu.publisher.place	Oxford	de
jgu.publisher.uri	http://dx.doi.org/10.1093/nar/gkw473	de
jgu.publisher.issn	1362-4962	de
jgu.publisher.issn	0305-1048	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
opus.date.modified	2018-08-23T08:26:03Z
opus.subject.dfgcode	00-000
opus.organisation.string	FB 09: Chemie, Pharmazie und Geowissenschaften: Institut für Pharmazie	de_DE
opus.identifier.opusid	56358
opus.institute.number	0908
opus.metadataonly	false
opus.type.contenttype	Keine	de_DE
opus.type.contenttype	None	en_EN
opus.affiliated	Kitsera, Nataliya
opus.affiliated	Epe, Bernd
opus.affiliated	Khobta, Andriy
jgu.publisher.doi	10.1093/nar/gkw473	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

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