Alkyladenine DNA glycosylase associates with transcription elongation to coordinate DNA repair with gene expression.
Chromatin
/ genetics
DNA Glycosylases
/ metabolism
DNA Methylation
DNA Repair
/ genetics
DNA-(Apurinic or Apyrimidinic Site) Lyase
/ genetics
Gene Expression
Gene Expression Regulation
/ genetics
Genomic Instability
HEK293 Cells
Humans
RNA Polymerase II
/ genetics
Transcription Elongation, Genetic
Transcriptional Elongation Factors
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 11 2019
29 11 2019
Historique:
received:
25
04
2019
accepted:
05
11
2019
entrez:
1
12
2019
pubmed:
1
12
2019
medline:
11
3
2020
Statut:
epublish
Résumé
Base excision repair (BER) initiated by alkyladenine DNA glycosylase (AAG) is essential for removal of aberrantly methylated DNA bases. Genome instability and accumulation of aberrant bases accompany multiple diseases, including cancer and neurological disorders. While BER is well studied on naked DNA, it remains unclear how BER efficiently operates on chromatin. Here, we show that AAG binds to chromatin and forms complex with RNA polymerase (pol) II. This occurs through direct interaction with Elongator and results in transcriptional co-regulation. Importantly, at co-regulated genes, aberrantly methylated bases accumulate towards the 3'end in regions enriched for BER enzymes AAG and APE1, Elongator and active RNA pol II. Active transcription and functional Elongator are further crucial to ensure efficient BER, by promoting AAG and APE1 chromatin recruitment. Our findings provide insights into genome stability maintenance in actively transcribing chromatin and reveal roles of aberrantly methylated bases in regulation of gene expression.
Identifiants
pubmed: 31784530
doi: 10.1038/s41467-019-13394-w
pii: 10.1038/s41467-019-13394-w
pmc: PMC6884549
doi:
Substances chimiques
Chromatin
0
Elp1 protein, human
0
Transcriptional Elongation Factors
0
RNA Polymerase II
EC 2.7.7.-
3-methyladenine-DNA glycosylase
EC 3.2.2.-
DNA Glycosylases
EC 3.2.2.-
APEX1 protein, human
EC 4.2.99.18
DNA-(Apurinic or Apyrimidinic Site) Lyase
EC 4.2.99.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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