| Literature DB >> 31784530 |
Nicola P Montaldo1,2, Diana L Bordin1, Alessandro Brambilla1, Marcel Rösinger2, Sarah L Fordyce Martin1, Karine Øian Bjørås1, Stefano Bradamante1, Per Arne Aas1, Antonia Furrer2,3, Lene C Olsen1,4,5, Nicolas Kunath1, Marit Otterlei1, Pål Sætrom1,4,5,6, Magnar Bjørås1,7, Leona D Samson8, Barbara van Loon9,10.
Abstract
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.Entities:
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Year: 2019 PMID： 31784530 PMCID： PMC6884549 DOI： 10.1038/s41467-019-13394-w
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919