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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Montaldo NP,Bordin DL,Brambilla A,Rösinger M,Fordyce Martin SL,Bjørås KØ,Bradamante S,Aas PA,Furrer A,Olsen LC,Kunath N,Otterlei M,Sætrom P,Bjørås M,Samson LD,van Loon Bdoi
10.1038/s41467-019-13394-wsubject
Has Abstractpub_date
2019-11-29 00:00:00pages
5460issue
1issn
2041-1723pii
10.1038/s41467-019-13394-wjournal_volume
10pub_type
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