Abstract:
:RECQL5 is a member of the highly conserved RecQ family of DNA helicases involved in DNA repair. RECQL5 interacts with RNA polymerase II (Pol II) and inhibits transcription of protein-encoding genes by an unknown mechanism. We show that RECQL5 contacts the Rpb1 jaw domain of Pol II at a site that overlaps with the binding site for the transcription elongation factor TFIIS. Our cryo-EM structure of elongating Pol II arrested in complex with RECQL5 shows that the RECQL5 helicase domain is positioned to sterically block elongation. The crystal structure of the RECQL5 KIX domain reveals similarities with TFIIS, and binding of RECQL5 to Pol II interferes with the ability of TFIIS to promote transcriptional read-through in vitro. Together, our findings reveal a dual mode of transcriptional repression by RECQL5 that includes structural mimicry of the Pol II-TFIIS interaction.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Kassube SA,Jinek M,Fang J,Tsutakawa S,Nogales Edoi
10.1038/nsmb.2596subject
Has Abstractpub_date
2013-07-01 00:00:00pages
892-9issue
7eissn
1545-9993issn
1545-9985pii
nsmb.2596journal_volume
20pub_type
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