Structural basis for DNA duplex separation by a superfamily-2 helicase

Buttner, K.; Nehring, Sebastian; Hopfner, Karl‐Peter

doi:10.1038/nsmb1246

Cited by 299 publications

(501 citation statements)

References 34 publications

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“…This strand‐separation mechanism is significantly different from that proposed for DNA helicases of the SF1A family (Velankar et al , 1999). However, it is reminiscent of the 3′‐5′ unwinding mechanism proposed for RNA helicases of the SF2 Ski2‐like family, where a structural element on the RecA2 domain (the β‐hairpin) inserts into the duplex and melts the incoming base pairs (Büttner et al , 2007). Melting elements on opposite sides of the helicase core together with the movements of the two RecA domains in response to ATP hydrolysis could thus underpin the opposite unwinding polarities of Upf1‐like and of Ski2‐like RNA helicases.…”

Section: Resultsmentioning

confidence: 99%

Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

et al. 2017

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The superfamily 1B (SF1B) helicase Sen1 is an essential protein that plays a key role in the termination of non‐coding transcription in yeast. Here, we identified the ~90 kDa helicase core of Saccharomyces cerevisiae Sen1 as sufficient for transcription termination in vitro and determined the corresponding structure at 1.8 Å resolution. In addition to the catalytic and auxiliary subdomains characteristic of the SF1B family, Sen1 has a distinct and evolutionarily conserved structural feature that “braces” the helicase core. Comparative structural analyses indicate that the “brace” is essential in shaping a favorable conformation for RNA binding and unwinding. We also show that subdomain 1C (the “prong”) is an essential element for 5′‐3′ unwinding and for Sen1‐mediated transcription termination in vitro. Finally, yeast Sen1 mutant proteins mimicking the disease forms of the human orthologue, senataxin, show lower capacity of RNA unwinding and impairment of transcription termination in vitro. The combined biochemical and structural data thus provide a molecular model for the specificity of Sen1 in transcription termination and more generally for the unwinding mechanism of 5′‐3′ helicases.

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Section: Resultsmentioning

confidence: 99%

Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

et al. 2017

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“…To interpret our data in this context, the structure of RECQ1 was aligned with those of 2 experimentally determined helicase-DNA complexes: HEL308 (PDB ID code 2P6R) (33), and PcrA (PBD ID code 3PJR) (39). The alignments were made as to maximize the overlap of the core ␤-strands of the 2 RecA-like domains (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structure of the human RECQ1 helicase reveals a putative strand-separation pin

Pike

Shrestha

Popuri

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

109

211

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RecQ-like helicases, which include 5 members in the human genome, are important in maintaining genome integrity. We present a crystal structure of a truncated form of the human RECQ1 protein with Mg-ADP. The truncated protein is active in DNA fork unwinding but lacks other activities of the full-length enzyme: disruption of Holliday junctions and DNA strand annealing. The structure of human RECQ1 resembles that of Escherichia coli RecQ, with some important differences. All structural domains are conserved, including the 2 RecA-like domains and the RecQ-specific zinc-binding and winged-helix (WH) domains. However, the WH domain is positioned at a different orientation from that of the E. coli enzyme. We identify a prominent ␤-hairpin of the WH domain as essential for DNA strand separation, which may be analogous to DNA strand-separation features of other DNA helicases. This hairpin is significantly shorter in the E. coli enzyme and is not required for its helicase activity, suggesting that there are significant differences between the modes of action of RecQ family members.DNA helicase ͉ DNA repair ͉ Holliday junction ͉ structural genomics ͉ winged helix T he RecQ helicases are a family of DNA-unwinding enzymes conserved from prokaryotes to mammals that play a key role in the maintenance of genome stability. The RecQ helicase family has 5 representatives in the human genome (1-3): RECQ1 (also known as RECQL or RECQL1), BLM, WRN, RECQ4, and RECQ5. Although these 5 enzymes are similar in their catalytic core, they probably have distinct functions, as indicated by the genetic disorders associated to mutations in the genes of BLM, WRN, and RECQ4. In particular, mutations in the gene encoding for BLM (4) are associated with the Bloom's syndrome (BS), which is manifested as an increased incidence of a wide spectrum of cancers. Werner's syndrome (WS), which is linked to mutations in the WRN (5) gene, involves many signs of premature aging, as well as a predisposition to a more limited spectrum of cancers. Mutations in the gene of RECQ4 are the cause of more varied genetic disease phenotypes, including Rothmund-Thomson (RTS) (6, 7), RAPADILINO (8), and Baller-Gerold (9) syndromes. No disease phenotypes have been associated with mutations in the genes of the other 2 family members, RECQ1 and RECQ5 yet, although they may be responsible for additional cancer predisposition disorders that are distinct from RTS, BS, and WS. In this regard, interesting candidates are patients with a phenotype similar to that of RTS individuals who do not carry any mutations in the RECQ4 gene (7). A possible role of RECQ1 in genome maintenance is suggested by several observations (reviewed in ref 10). Biochemical purification from human embryonic kidney cells recovered RECQ1 as the major Holliday junction (HJ) branch migration activity (11). Knockout of the RECQ1 gene in mice (12) or suppression of its expression in HeLa cells (11) resulted in cellular phenotypes that include chromosomal instability, increased sister chromatid exchange, and hei...

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“…The bound ssDNA is in a configuration more similar to that found in a DNA duplex, with the bases stacked against one another, unlike the extended conformation observed in PcrA. Interestingly, the RecD2 mode of binding is more similar to that seen in SF2 enzymes such as NS3, Rad54, Vasa, and Hel308 [104,[123][124][125] rather than SF1A helicases [126].…”

Section: Structure Of Sf1b Helicases (Recd2 and Dda)mentioning

confidence: 86%

Erratum to: Structure and Mechanisms of SF1 DNA Helicases

Raney

Byrd

Aarattuthodiyil

2012

Advances in Experimental Medicine and Biology

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Superfamily I is a large and diverse group of monomeric and dimeric helicases defined by a set of conserved sequence motifs. Members of this class are involved in essential processes in both DNA and RNA metabolism in all organisms. In addition to conserved amino acid sequences, they also share a common structure containing two RecA-like motifs involved in ATP binding and hydrolysis and nucleic acid binding and unwinding. Unwinding is facilitated by a "pin" structure which serves to split the incoming duplex. This activity has been measured using both ensemble and single-molecule conditions. SF1 helicase activity is modulated through interactions with other proteins.

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Structural basis for DNA duplex separation by a superfamily-2 helicase

Cited by 299 publications

References 34 publications

Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

Structure of the human RECQ1 helicase reveals a putative strand-separation pin

Erratum to: Structure and Mechanisms of SF1 DNA Helicases

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