title: Interaction of Saccharomyces cerevisiae HMO2 domains with distorted DNA.
abstract: The Saccharomyces cerevisiae high mobility  group protein HMO2 is a component of the chromatin remodeling complex INO80. In this capacity, it has been shown to direct INO80 to DNA double-strand breaks, thereby contributing to double-strand break repair. Consistent with such function, HMO2 binds DNA ends, protecting them from exonucleolytic degradation. We show here that both domains of HMO2, HMO2-BoxA and HMO2-BoxB, bind preferentially to distorted DNA, with HMO2-BoxA binding preferentially to four-way DNA junctions and DNA with tandem mismatches and HMO2-BoxB binding four-way junctions as well as DNA with stem-loop structures, tandem mismatches, and abasic sites. As previously reported for mammalian high mobility  group proteins, the acidic C-terminal extension significantly attenuates DNA binding. Notably, the unique ability of HMO2 to protect DNA ends is conferred by the Box A domain. Considering the reported roles for INO80 in other events such as recovery of stalled replication forks and nucleotide excision repair, we assessed the effect of DNA damaging agents on an hmo2Δ strain; while modest growth inhibition is seen upon exposure to UV light, exposure to hydroxyurea, which causes replication fork arrest, induces severe growth deficiency. These data suggest that HMO2 may also participate in directing the INO80 complex to sites such as stalled replication forks; the preferred binding of HMO2 domains to damaged DNA and intermediates in homologous recombination is consistent with such function.
authors.affiliation: Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Sreerupa
authors.initials: S
authors.lastname: Ray
authors.forename: Anne
authors.initials: A
authors.lastname: Grove
mesh_terms: D001665:Binding Sites; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004271:DNA, Fungal / Q000737:chemistry* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006609:High Mobility Group Proteins / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D004271:DNA, Fungal; D006609:High Mobility Group Proteins; C529112:NHP10 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins