Skip to main content
SpringerLink
Log in

Hrq1 facilitates nucleotide excision repair of DNA damage induced by 4-nitroquinoline-1-oxide and cisplatin in Saccharomyces cerevisiae

  • Microbial Genetics, Genomics and Molecular Biology
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ashton, T.M. and Hickson, I.D. 2010. Yeast as a model system to study RecQ helicase function. DNA Repair (Amst) 9, 303–314.

    Article  CAS  Google Scholar 

  • Barea, F., Tessaro, S., and Bonatto, D. 2008. In silico analyses of a new group of fungal and plant RecQ4-homologous proteins. Comput. Biol. Chem. 32, 349–358.

    Article  PubMed  CAS  Google Scholar 

  • Baudin, A., Ozier-Kalogeropoulos, O., Denouel, A., Lacroute, F., and Cullin, C. 1993. A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res. 21, 3329–3330.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bernstein, K.A., Gangloff, S., and Rothstein, R. 2010. The RecQ DNA helicases in DNA repair. Annu. Rev. Genet. 44, 393–417.

    Article  PubMed  CAS  Google Scholar 

  • Blastyák, A., Pintér, L., Unk, I., Prakash, L., Prakash, S., and Haracska, L. 2007. Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression. Mol. Cell 28, 167–175.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bohr, V.A. 2008. Rising from the RecQ-age: the role of human RecQ helicases in genome maintenance. Trends Biochem. Sci. 33, 609–620.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Choi, D.H., Lee, R., Kwon, S.H., and Bae, S.H. 2013. Hrq1 functions independently of Sgs1 to preserve genome integrity in Saccharomyces cerevisiae. J. Microbiol. 51, 105–112.

    Article  PubMed  CAS  Google Scholar 

  • Chris, K., Michaelis, S., and Mitchell, A. 1994. Methods in yeast genetics. pp. 207–217. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, N.Y., USA.

    Google Scholar 

  • Chu, W.K. and Hickson, I.D. 2009. RecQ helicases: multifunctional genome caretakers. Nat. Rev. Cancer 9, 644–654.

    Article  PubMed  CAS  Google Scholar 

  • Coin, F., Proietti De Santis, L., Nardo, T., Zlobinskaya, O., Stefanini, M., and Egly, J.M. 2006. p8/TTD-A as a repair-specific TFIIH subunit. Mol. Cell 21, 215–226.

    Article  PubMed  CAS  Google Scholar 

  • Compe, E. and Egly, J.M. 2012. TFIIH: when transcription met DNA repair. Nat. Rev. Mol. Cell Biol. 13, 343–354.

    Article  PubMed  CAS  Google Scholar 

  • Evans, E., Moggs, J.G., Hwang, J.R., Egly, J.M., and Wood, R.D. 1997. Mechanism of open complex and dual incision formation by human nucleotide excision repair factors. EMBO J. 16, 6559–6573.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Fan, W. and Luo, J. 2008. RecQ4 facilitates UV light-induced DNA damage repair through interaction with nucleotide excision repair factor xeroderma pigmentosum group A (XPA). J. Biol. Chem. 283, 29037–29044.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Groocock, L.M., Prudden, J., Perry, J.J., and Boddy, M.N. 2012. The RecQ4 orthologue Hrq1 is critical for DNA interstrand cross-link repair and genome stability in fission yeast. Mol. Cell Biol. 32, 276–287.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Guzder, S.N., Sommers, C.H., Prakash, L., and Prakash, S. 2006. Complex formation with damage recognition protein Rad14 is essential for Saccharomyces cerevisiae Rad1-Rad10 nuclease to perform its function in nucleotide excision repair in vivo. Mol. Cell Biol. 26, 1135–1141.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ide, F., Oda, H., Nakatsuru, Y., Kusama, K., Sakashita, H., Tanaka, K., and Ishikawa, T. 2001. Xeroderma pigmentosum group A gene action as a protection factor against 4-nitroquinoline 1-oxide-induced tongue carcinogenesis. Carcinogenesis 22, 567–572.

    Article  PubMed  CAS  Google Scholar 

  • James, P., Halladay, J., and Craig, E.A. 1996. Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics 144, 1425–1436.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kwon, S.H., Choi, D.H., Lee, R., and Bae, S.H. 2012. Saccharomyces cerevisiae Hrq1 requires a long 3 -tailed DNA substrate for helicase activity. Biochem. Biophys. Res. Commun. 427, 623–628.

    Article  PubMed  CAS  Google Scholar 

  • Lafrance-Vanasse, J., Arseneault, G., Cappadocia, L., Legault, P., and Omichinski, J.G. 2013. Structural and functional evidence that Rad4 competes with Rad2 for binding to the Tfb1 subunit of TFIIH in NER. Nucleic Acids Res. 41, 2736–2745.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lee, K.Y. and Myung, K. 2008. PCNA modifications for regulation of post-replication repair pathways. Mol. Cells 26, 5–11.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lejeune, D., Chen, X., Ruggiero, C., Berryhill, S., Ding, B., and Li, S. 2009. Yeast Elc1 plays an important role in global genomic repair but not in transcription coupled repair. DNA Repair (Amst) 8, 40–50.

    Article  CAS  Google Scholar 

  • Li, S. and Smerdon, M.J. 2004. Dissecting transcription-coupled and global genomic repair in the chromatin of yeast GAL1-10 genes. J. Biol. Chem. 279, 14418–14426.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lok, B.H. and Powell, S.N. 2012. Molecular pathways: understanding the role of Rad52 in homologous recombination for therapeutic advancement. Clin. Cancer Res. 18, 6400–6406.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Maher, R.L., Branagan, A.M., and Morrical, S.W. 2011. Coordination of DNA replication and recombination activities in the maintenance of genome stability. J. Cell Biochem. 112, 2672–2682.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mardiros, A., Benoun, J.M., Haughton, R., Baxter, K., Kelson, E.P., and Fischhaber, P.L. 2011. Rad10-YFP focus induction in response to UV depends on RAD14 in yeast. Acta Histochem. 113, 409–415.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • McVey, M. 2010. Strategies for DNA interstrand crosslink repair: insights from worms, flies, frogs, and slime molds. Environ. Mol. Mutagen. 51, 646–658.

    PubMed  CAS  Google Scholar 

  • Monnat, R.J. Jr. 2010. Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology. Semin. Cancer Biol. 20, 329–339.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Oksenych, V. and Coin, F. 2010. The long unwinding road: XPB and XPD helicases in damaged DNA opening. Cell Cycle 9, 90–96.

    Article  PubMed  CAS  Google Scholar 

  • Paques, F. and Haber, J.E. 1999. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 63, 349–404.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Prakash, S. and Prakash, L. 2000. Nucleotide excision repair in yeast. Mutat. Res. 451, 13–24.

    Article  PubMed  CAS  Google Scholar 

  • Riedl, T., Hanaoka, F., and Egly, J.M. 2003. The comings and goings of nucleotide excision repair factors on damaged DNA. EMBO J. 22, 5293–5303.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sikorski, R.S. and Hieter, P. 1989. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122, 19–27.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sugawara, N., Wang, X., and Haber, J.E. 2003. In vivo roles of Rad52, Rad54, and Rad55 proteins in Rad51-mediated recombination. Mol. Cell 12, 209–219.

    Article  PubMed  CAS  Google Scholar 

  • Tsodikov, O.V., Ivanov, D., Orelli, B., Staresincic, L., Shoshani, I., Oberman, R., Scharer, O.D., Wagner, G., and Ellenberger, T. 2007. Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA. EMBO J. 26, 4768–4776.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Verhage, R., Zeeman, A.M., de Groot, N., Gleig, F., Bang, D.D., van de Putte, P., and Brouwer, J. 1994. The RAD7 and RAD16 genes, which are essential for pyrimidine dimer removal from the silent mating type loci, are also required for repair of the nontranscribed strand of an active gene in Saccharomyces cerevisiae. Mol. Cell. Biol. 14, 6135–6142.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Williams, A.B., Hetrick, K.M., and Foster, P.L. 2010. Interplay of DNA repair, homologous recombination, and DNA polymerases in resistance to the DNA damaging agent 4-nitroquinoline-1-oxide in Escherichia coli. DNA Repair (Amst) 9, 1090–1097.

    Article  CAS  Google Scholar 

  • Zhang, W., Qin, Z., Zhang, X., and Xiao, W. 2011. Roles of sequential ubiquitination of PCNA in DNA-damage tolerance. FEBS Lett. 585, 2786–2794.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological Sciences, College of Natural Science, Inha University, Incheon, 402-751, Republic of Korea

    Do-Hee Choi, Moon-Hee Min, Min-Ji Kim, Rina Lee, Sung-Hun Kwon & Sung-Ho Bae

Authors
  1. Do-Hee Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moon-Hee Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min-Ji Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rina Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sung-Hun Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sung-Ho Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung-Ho Bae.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, DH., Min, MH., Kim, MJ. et al. Hrq1 facilitates nucleotide excision repair of DNA damage induced by 4-nitroquinoline-1-oxide and cisplatin in Saccharomyces cerevisiae . J Microbiol. 52, 292–298 (2014). https://doi.org/10.1007/s12275-014-4018-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-014-4018-z

Keywords

Search

Navigation