title: Substrate-selective repair and restart of replication forks by DNA translocases.
abstract: Stalled replication forks are sources of genetic instability. Multiple fork-remodeling enzymes are recruited to stalled forks, but how they work to promote fork restart is poorly understood. By combining ensemble biochemical assays and single-molecule studies with magnetic tweezers, we show that SMARCAL1 branch migration and DNA-annealing activities are directed by the single-stranded DNA-binding protein RPA to selectively regress stalled replication forks caused by blockage to the leading-strand polymerase and to restore normal replication forks with a lagging-strand gap. We unveil the molecular mechanisms by which RPA enforces SMARCAL1 substrate preference. E. coli RecG acts similarly to SMARCAL1 in the presence of E. coli SSB, whereas the highly related human protein ZRANB3 has different substrate preferences. Our findings identify the important substrates of SMARCAL1 in fork repair, suggest that RecG and SMARCAL1 are functional orthologs, and provide a comprehensive model of fork repair by these DNA translocases.
authors.affiliation: Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Rémy
authors.initials: R
authors.lastname: Bétous
authors.forename: Frank B
authors.initials: FB
authors.lastname: Couch
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Mason
authors.forename: Brandt F
authors.initials: BF
authors.lastname: Eichman
authors.forename: Maria
authors.initials: M
authors.lastname: Manosas
authors.forename: David
authors.initials: D
authors.lastname: Cortez
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D057809:HEK293 Cells; D006801:Humans; D007313:Insecta / Q000166:cytology / Q000821:virology; D011485:Protein Binding; D018741:Replication Origin; D013698:Templates, Genetic
chemical_list: D004247:DNA; C412482:SMARCAL1 protein, human; D004265:DNA Helicases