Publication Type:

Journal Article

Source:

Molecular and Cellular Biology, Volume 32, Number 2, p.276-287 (2012)

URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84856794104&partnerID=40&md5=77cff5dd84bcfeb1a7b5c8051325b4d7

Keywords:

3' untranslated region, 5' untranslated region, Amino Acid Motifs, article, cell viability, cisplatin, controlled study, Cross-Linking Reagents, DNA, DNA cross linking, DNA damage, DNA Helicases, DNA repair, enzyme activity, enzyme substrate, excision repair, Fungal, Gene Expression Regulation, Genes, genetic epistasis, genomic instability, Hrq1 protein, intracellular signaling, mms2 protein, Mutation, nonhuman, nucleic acid binding protein, PCNA protein, priority journal, protein analysis, recombination repair, RecQ helicase, RecQ Helicases, RecQ4 protein, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, ubiquitin conjugating enzyme 13, ultraviolet radiation, unclassified drug, 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 hyperrecombinant and mutator phenotypes; analogous defects may underlie the genetic instability and diseases associated with RecQ4 dysfunction. © 2012, American Society for Microbiology.

Notes:

cited By (since 1996)4

Cite this Research Publication

L. Ma Groocock, Prudden, Ja, Perry, J. J. Pab, and Boddy, M. Na, “The RecQ4 orthologue Hrq1 is critical for DNA interstrand cross-link repair and genome stability in fission yeast”, Molecular and Cellular Biology, vol. 32, pp. 276-287, 2012.