HARP is an ATP-driven annealing helicase.
DNA-dependent adenosine triphosphatases (ATPases) participate in a broad range of biological processes including transcription, DNA repair, and chromatin dynamics. Mutations in the HepA-related protein (HARP) ATPase are responsible for Schimke immuno-osseous dysplasia (SIOD), but the function of the protein is unknown. We found that HARP is an ATP-dependent annealing helicase that rewinds single-stranded DNA bubbles that are stably bound by replication protein A. Other related ATPases, including the DNA translocase Rad54, did not exhibit annealing helicase activity. Analysis of mutant HARP proteins suggests that SIOD is caused by a deficiency in annealing helicase activity. Moreover, the pleiotropy of HARP mutations is consistent with the function of HARP as an annealing helicase that acts throughout the genome to oppose the action of DNA-unwinding activities in the nucleus.
Yusufzai
Timur
T
Section of Molecular Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Kadonaga
James T
JT
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D004265:DNA Helicases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D050505:Mutant Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009690:Nucleic Acid Conformation; D010009:Osteochondrodysplasias / Q000235:genetics; D051716:Replication Protein A / Q000378:metabolism; D013577:Syndrome
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D050505:Mutant Proteins; D009687:Nuclear Proteins; D051716:Replication Protein A; D000255:Adenosine Triphosphate; C412482:SMARCAL1 protein, human; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C103532:RAD54L protein, human