title: Hrq1 facilitates nucleotide excision repair of DNA damage induced by 4-nitroquinoline-1-oxide and cisplatin in Saccharomyces cerevisiae.
abstract: Hrq1 helicase is a novel member of the RecQ family. Among the five human RecQ helicases, Hrq1 is most homologous to RECQL4 and is conserved in fungal genomes. Recent genetic and biochemical studies have shown that it is a functional gene, involved in the maintenance of genome stability. To better define the roles of Hrq1 in yeast cells, we investigated genetic interactions between HRQ1 and several DNA repair genes. Based on DNA damage sensitivities induced by 4-nitroquinoline-1-oxide (4-NQO) or cisplatin, RAD4 was found to be epistatic to HRQ1. On the other hand, mutant strains defective in either homologous recombination (HR) or post-replication repair (PRR) became more sensitive by additional deletion of HRQ1, indicating that HRQ1 functions in the RAD4-dependent nucleotide excision repair (NER) pathway independent of HR or PRR. In support of this, yeast two-hybrid analysis showed that Hrq1 interacted with Rad4, which was enhanced by DNA damage. Overexpression of Hrq1K318A helicase-deficient protein rendered mutant cells more sensitive to 4-NQO and cisplatin, suggesting that helicase activity is required for the proper function of Hrq1 in NER.
authors.affiliation: Department of Biological Sciences, College of Natural Science, Inha University, Incheon, 402-751, Republic of Korea.
authors.forename: Do-Hee
authors.initials: DH
authors.lastname: Choi
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Min
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Kim
authors.forename: Rina
authors.initials: R
authors.lastname: Lee
authors.forename: Sung-Hun
authors.initials: SH
authors.lastname: Kwon
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Bae
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D009153:Mutagens / Q000633:toxicity; D025941:Protein Interaction Mapping; D053484:RecQ Helicases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D015112:4-Nitroquinoline-1-oxide; C579040:Hrq1 protein, S cerevisiae; D053484:RecQ Helicases; D002945:Cisplatin