2015
DOI: 10.1074/jbc.m115.674002
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Saccharomyces cerevisiae Sen1 Helicase Domain Exhibits 5′- to 3′-Helicase Activity with a Preference for Translocation on DNA Rather than RNA

Abstract: Background: Yeast Sen1 helicase and its human ortholog senataxin promote accurate transcription termination. Results: Sen1 helicase domain exhibits 5Ј-to 3Ј-helicase activity on DNA and RNA and binds endogenous RNA. Conclusion: Biochemical activities of purified Sen1 helicase domain are consistent with its proposed function in resolving cotranscriptional R-loops. Significance: Mutations in senataxin and its paralog IGHMBP2 cause crippling neurodegenerative diseases.

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Cited by 53 publications
(49 citation statements)
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“…For structural studies, we expressed and purified a fragment of Sen1 encompassing residues 1,095–1,904 (hereafter referred to as Sen1 Hel ), with the shorter N‐terminus previously identified by the Brow's group (Martin‐Tumasz & Brow, 2015). Sen1 Hel showed levels of RNA‐dependent ATPase activity similar to those of full‐length Sen1 purified from yeast (ySen1 FL).…”
Section: Resultsmentioning
confidence: 99%
“…For structural studies, we expressed and purified a fragment of Sen1 encompassing residues 1,095–1,904 (hereafter referred to as Sen1 Hel ), with the shorter N‐terminus previously identified by the Brow's group (Martin‐Tumasz & Brow, 2015). Sen1 Hel showed levels of RNA‐dependent ATPase activity similar to those of full‐length Sen1 purified from yeast (ySen1 FL).…”
Section: Resultsmentioning
confidence: 99%
“…It was recently proposed that the Mfd translocase in Escherichia coli could both nudge forward weakly paused RNAP and induce the dissociation of stalled RNAP using a release and catch-up mechanism (Le et al, 2018). However, the molecular mechanisms involved in such a release and catch-up mechanism might differ between Sen1 and Mfd, because Mfd was shown to translocate autonomously on double-stranded DNA, whereas both budding yeast and fission yeast Sen1 were shown to translocate on both single-stranded DNA and RNA, albeit at greater rate on DNA (Kim et al, 1999;Martin-Tumasz & Brow, 2015;Han et al, 2017). Importantly, the release and catch-up mechanism was also proposed to underlie the role of Mfd in both transcriptioncoupled repair and transcription-replication conflict resolution (Le et al, 2018) and budding yeast Sen1 has also been implicated in both transcription-coupled repair and transcriptionreplication conflict resolution (Mischo et al, 2011;Alzu et al, 2012;Brambati et al, 2018), strengthening the analogy with Mfd.…”
Section: Lack Of Sen1 Impacts Rnap3 Trna Levelsmentioning
confidence: 99%
“…However, the mechanisms involved probably differ in both species as budding yeast Sen1 contributes to RNAP2 transcription termination as part of the Nrd1-Nab3-Sen1 (NNS) complex, which is not conserved in human cells. Both budding and fission yeast Sen1 can translocate in a 5 0 -3 0 direction on either single-stranded DNA or RNA in vitro (Kim et al, 1999;Martin-Tumasz & Brow, 2015;Han et al, 2017), and it is believed that long, co-transcriptional RNA-DNA hybrids (also known as R-loops) represent a critical substrate of budding yeast Sen1 and human Senataxin in vivo (Mischo et al, 2011;Skourti-Stathaki et al, 2011 andreviewed in Groh et al, 2017). Both budding and fission yeast Sen1 can translocate in a 5 0 -3 0 direction on either single-stranded DNA or RNA in vitro (Kim et al, 1999;Martin-Tumasz & Brow, 2015;Han et al, 2017), and it is believed that long, co-transcriptional RNA-DNA hybrids (also known as R-loops) represent a critical substrate of budding yeast Sen1 and human Senataxin in vivo (Mischo et al, 2011;Skourti-Stathaki et al, 2011 andreviewed in Groh et al, 2017).…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…In both cases the reaction can be fully recapitulated in vitro with purified components, demonstrating that a simple system containing only the helicase and the elongation complex is sufficient for transcription termination. Sen1 (like Rho) is an active helicase [83,84] and has been implicated in unwinding DNA:RNA hybrids (R loops) [85], but whether termination requires translocation on the nascent RNA and/or unwinding of nucleic acids duplexes is unclear. Deciphering whether Sen-1 dependent termination involves hybrid shearing, hyper-translocation or an allosteric change, as proposed for bacterial termination, remains a challenge for future studies.…”
Section: Nns Pathwaymentioning
confidence: 99%