Hrq1 facilitates repair of 4-NQO and cisplatin-induced DNA damage via nucleotide excision repair

초록

RecQ helicases are highly conserved in all living organisms and play important roles in maintenance of genome stability. Recent bioinformatic analyses revealed the presence of a novel RecQ helicase, Hrq1, in fungal genomes. Previously we reported that Hrq1 is an active helicase and functions in repair of DNA damage induced by 4-NQO and cisplatin. To investigate the precise role of Hrq1 in DNA repair pathways, we investigated the genetic interactions between Hrq1 and various genes involved in homologous recombination, post-replication repair, and nucleotide excision repair pathways. Based on DNA damage sensitivities, we found that only RAD4 was epistatic to HRQ1, which suggest that Hrq1 functions downstream of nucleotide excision repair. Dominant negative effect of Hrq1K318A mutant also showed consistent genetic profile. We also found that Hrq1 interacts with Rad14, a key protein involved in nucleotide excision repair, in yeast two hybrid assay. Furthermore, the interaction was enhanced in response to treatments of 4-NQO or cisplatin. These findings suggest that Hrq1 may be directly involved in nucleotide excision repair pathway.