title: The RecQ4 orthologue Hrq1 is critical for DNA interstrand cross-link repair and genome stability in fission yeast.
abstract: Of the five human RecQ family helicases, RecQ4, BLM, and WRN suppress distinct genome instability-linked diseases with severe phenotypes, often with indeterminate etiologies. Here, we functionally define Hrq1, a novel orthologue of RecQ4 from fission yeast. Biochemical analysis of Hrq1 reveals a DEAH box- and ATP-dependent 3'-5' helicase activity on various DNA substrates, including bubbles but not blunt duplexes, characteristic of the RecQ family. Cells lacking Hrq1 suffer spontaneous genomic instability and, consequently, require homologous recombination repair and the DNA damage checkpoint for viability. Hrq1 supports the nucleotide excision repair of DNA damage caused by the chemotherapeutic agent cisplatin and, in certain genetic contexts, UV light. Genetic epistasis analyses reveal that Hrq1 acts parallel to the PCNA/Ubc13/Mms2-dependent postreplication repair (PRR) pathway. Thus, in hrq1Δ cells, lesions are channeled through the PRR pathway, yielding hyper-recombinant and mutator phenotypes; analogous defects may underlie the genetic instability and diseases associated with RecQ4 dysfunction.
authors: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Lynda M
authors: LM
authors: Groocock
authors: John
authors: J
authors: Prudden
authors: J Jefferson P
authors: JJ
authors: Perry
authors: Michael N
authors: MN
authors: Boddy
mesh_terms: D020816:Amino Acid Motifs; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D042822:Genomic Instability / Q000187:drug effects; D009154:Mutation; D053484:RecQ Helicases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000737:chemistry / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D004271:DNA, Fungal; D029702:Schizosaccharomyces pombe Proteins; C570107:Hrq1 protein, S pombe; D004265:DNA Helicases; D053484:RecQ Helicases; C106462:Rqh1 protein, S pombe; D002945:Cisplatin