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Review
. 2020 Feb 18;11(2):205.
doi: 10.3390/genes11020205.

Maintenance of Yeast Genome Integrity by RecQ Family DNA Helicases

Sonia Vidushi Gupta  1 , Kristina Hildegard Schmidt  1   2
Affiliations
Review

Maintenance of Yeast Genome Integrity by RecQ Family DNA Helicases

Sonia Vidushi Gupta et al. Genes (Basel). .

Abstract

With roles in DNA repair, recombination, replication and transcription, members of the RecQ DNA helicase family maintain genome integrity from bacteria to mammals. Mutations in human RecQ helicases BLM, WRN and RecQL4 cause incurable disorders characterized by genome instability, increased cancer predisposition and premature adult-onset aging. Yeast cells lacking the RecQ helicase Sgs1 share many of the cellular defects of human cells lacking BLM, including hypersensitivity to DNA damaging agents and replication stress, shortened lifespan, genome instability and mitotic hyper-recombination, making them invaluable model systems for elucidating eukaryotic RecQ helicase function. Yeast and human RecQ helicases have common DNA substrates and domain structures and share similar physical interaction partners. Here, we review the major cellular functions of the yeast RecQ helicases Sgs1 of Saccharomyces cerevisiae and Rqh1 of Schizosaccharomyces pombe and provide an outlook on some of the outstanding questions in the field.

Keywords: RecQ helicases; Rqh1; Sgs1; genome instability; yeast.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Conserved domain structure of RecQ helicases from major model systems. RecQ helicases are conserved from bacteria to mammals. Proteins are aligned by their conserved helicase domains. The respective organism is shown on the left and the protein length in amino acids is indicated on the right. Human RECQ5α, RECQ5β and RECQ5γ are isoforms resulting from alternative splicing of the RECQ5 gene.
Figure 2
Figure 2
Structure of Sgs1 and its binding partners. Sgs1 is composed of the structurally ordered ATPase/helicase core and HRDC domains in the C-terminal half of the protein and a 645-residue long intrinsically disordered N-terminal tail. This domain structure is conserved in human BLM and several other RecQ family helicases. In addition to SUMOylation at K621, SUMOylation at K175 and K831 has also been reported [54]. Pink boxes indicate phosphorylation sites. The helicase core contains the ATPase domain, consisting of two RecA-like lobes, 1A and 2A, which harbor the eight RecQ conserved helicase motifs indicated in black (motifs 0 to VI), and the RQC-domain, consisting of the zinc-binding and winged-helix subdomains. For interacting proteins, the binding region in Sgs1 is shown in brackets after the protein name, followed by the assay of detection. Interacting proteins for which binding sites on Sgs1 have not been narrowed down are listed in the gray box. SE, strand-exchange domain; SIMs, SUMO-interacting motifs; RQC, RecQ-C-terminal domain; HRDC, helicase-and-RNaseD-like-C-terminal domain; Y2H, yeast-two-hybrid assay; co-IP, co-immunoprecipitation; ITC, isothermal titration calorimetry.
Figure 3
Figure 3
Structure of Rqh1. Rqh1 shares the ATPase/helicase, RQC and HRDC domains with Sgs1 and other RecQ helicases [78]. Red boxes indicate predicted SUMOylation sites with residues 724-727 (PKKD) being the predominant site. Pink boxes represent phosphorylation sites [76,77].
Figure 4
Figure 4
DNA substrates that Sgs1 binds and unwinds. Sgs1 preferentially unwinds Holliday junctions in vitro and G4 quadruplex DNA with more efficiency than duplex DNA. It can displace the D-loop formed during strand invasion and also unwind forked and ssDNA overhang structures.
Figure 5
Figure 5
Genetic interactions of SGS1. Negative genetic interactions of the SGS1 deletion mutation sgs1Δ are shown in red. Mutants that are rescued by sgs1Δ are shown in green, and mutations that rescue the sgs1Δ mutant are shown in blue. Orange, red, green and gray circles group genes involved in DNA repair, DNA damage and replication stress checkpoints, replication, and ‘other’ functions, respectively. Genetic interactions are primarily based on growth rates, hypersensitivity to DNA-damaging agents, DNA resection rates, mutation frequencies and checkpoint activation.
Figure 6
Figure 6
Early and late roles for Sgs1 in DSB repair by homologous recombination. In addition to long-range resection and double-Holliday-junction dissolution, Sgs1-Top3-Rmi1 has also been implicated in D-loop reversal. Genetic evidence suggests that the Sgs1-Rad51 interaction promotes homologous recombination; a model has been proposed wherein the acidic region of Sgs1 acts as a DNA mimic that can compete with ssDNA for RPA binding, thereby facilitating initial loading of Rad51 [57]. Shu complex proteins promote Rad51 filament formation by antagonizing the antirecombinase Srs2 and by interacting with Rad51-Rad55-Rad57 [148,149,150].
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