title: Identification of a Substrate Recognition Domain in the Replication Stress Response Protein Zinc Finger Ran-binding Domain-containing Protein 3 (ZRANB3).
abstract: DNA damage and other forms of replication stress can cause replication forks to stall. Replication stress response proteins stabilize and resolve stalled forks by mechanisms that include fork remodeling to facilitate repair or bypass of damaged templates. Several enzymes including SMARCAL1, HLTF, and ZRANB3 catalyze these reactions. SMARCAL1 and HLTF utilize structurally distinct accessory domains attached to an ATPase motor domain to facilitate DNA binding and catalysis of fork remodeling reactions. Here we describe a substrate recognition domain within ZRANB3 that is needed for it to recognize forked DNA structures, hydrolyze ATP, catalyze fork remodeling, and act as a structure-specific endonuclease. Thus, substrate recognition domains are a common feature of fork remodeling, SNF2-family, DNA-dependent ATPases, and our study provides further mechanistic understanding of how these enzymes maintain genome integrity during DNA replication.
authors.affiliation: From the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 and.
authors.forename: Akosua
authors.initials: A
authors.lastname: Badu-Nkansah
authors.affiliation: Department of Biological Sciences, Vanderbilt University College of Arts and Sciences, Nashville, Tennessee 37232.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Mason
authors.affiliation: From the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 and Department of Biological Sciences, Vanderbilt University College of Arts and Sciences, Nashville, Tennessee 37232.
authors.forename: Brandt F
authors.initials: BF
authors.lastname: Eichman
authors.affiliation: From the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 and david.cortez@vanderbilt.edu.
authors.forename: David
authors.initials: D
authors.lastname: Cortez
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases / Q000737:chemistry* / Q000378:metabolism*; D004260:DNA Repair; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D000255:Adenosine Triphosphate; D004247:DNA; D004265:DNA Helicases; C555409:ZRANB3 protein, human
keywords: DNA; DNA damage response; DNA repair; DNA replication; DNA-binding protein; endonuclease; protein domain