The role of DNA polymerase alpha in the control of mutagenesis in Saccharomyces cerevisiae cells starved for nutrients

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract


In nature, microorganisms experience numerous environmental stresses and generally grow poorly most of the time. In the last two decades it has become evident that mutations arise not only in actively dividing cells but also in nonreplicating or slowly replicating cells starved for nutrients. In yeast, precise base selection and proofreading by replicative DNA polymerases δ and ε keep starvation-associated mutagenesis (SAM) at basal levels. Less is known about the role of replicative DNA polymerase α (Pol α). Here we provide evidence that Pol α is involved in the control of SAM in yeast cells starved for adenine by participation in sporadic replication and/or DNA repair under these conditions. 

About the authors

Nora Babudri

University of Perugia, Perugia, Italy

Email: babudri@upihg.it

Alessandro Achilli

University of Pavia, Pavia, Italy

Email: achilli@unipg.it.

Chiara Martinelli

University of Pavia, Pavia, Italy

Email: chiaramartinelli@hotmail.it.

Elizabeth Moore

University of Nebraska, Linkoln, NE, USA

Email: eamoore@unmc.edu.

Hovirag Lancioni

University of Pavia, Pavia, Italy

Email: lancioni@kataweb.com

Yuri I Pavlov

Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE, USA

Email: ypavlov@unmc.edu

References

  1. Achilli A., Matmati N., Casalone E. et al., 2004. The exceptionally high rate of spontaneous mutations in the polymerase δ proofreading exonuclease-deficient Saccharomyces cerevisiae strain starved for adenine//BMC Genetics. Vol. 5. P. 34-44.
  2. Amberg D. C., Burke D., Strathern J., 2005. Methods in Yeast Genetics: a Cold Spring Harbor Laboratory Course Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
  3. Babudri N., Lucaccioni A., Achilli A., 2006. Adaptive mutagenesis in the yeast Saccharomyces cerevisiae//Ecol. Genet. Vol. 4. P. 20-28.
  4. Babudri N., Pavlov Y. I., Matmati N. et al., 2001. Stationaryphase mutations in proofreading exonuclease-deficient strainsof Saccharomyces cerevisiae//Mol. Genet. Genomics.Vol. 265. P. 362-366.
  5. Bullock P. A., Seo Y. S., Hurwitz J., 1991. Initiation of simian virus 40 DNA synthesis in vitro//Mol. Cell. Biol. Vol. 11. P. 2350-2361.
  6. Büttner S., Eisenberg T., Herker E. et al., 2006. Why yeast cells can undergo apoptosis: death in time of peace, love, war//Journ. Cell. Biol. Vol. 175. P. 521-525.
  7. Cairns J., 1993. Directed mutation//Science. Vol. 260. P. 1221-1224.
  8. Deem A., Barker K., VanHulle K. et al., 2008. Defective break-induced replication leads to half-crossovers in Saccharomycese cerevisiae//Genetics. Vol. 179. P. 1845-1860.
  9. Forsburg S. L., 2001. The art and design of genetic screens: yeast//Nat. Rev. Genet. Vol. 2. P. 659-668.
  10. Foster P. L., 2007. Stress-induced mutagenesis in bacteria//Crit. Rev. Biochem. Mol. Biol. Vol. 42. P. 373-379.
  11. Garg P., Burgers P., 2005. DNA polymerases that propagate the eukaryotic DNA replication Fork//Crit. Rev. Biochem. Mol. Biol. Vol. 40. P. 115-128.
  12. Gutierrez P. J., Wang T. S., 2003. Genomic instability induced by mutations in Saccharomyces cerevisiae POL1//Genetics. Vol. 165. P. 65-81.
  13. Halas A., Baranowska H., Podlaska A., 2009. Evaluation of the roles of Pol zeta and NHEJ in starvation-associated spontaneous mutagenesis in the yeast Saccharomyces cerevisiae//Curr. Genet. Vol. 55. P. 245-251.
  14. Hall B. G., 1992. Selection-induced mutations occur in yeast//Proc. Natl. Acad. Sci. USA. Vol. 89. P. 4300-4303.
  15. Heidenreich E., 2007. Adaptive mutation in Saccharomyces cerevisiae//Critical. Rev. Biochem. Mol. Biol. Vol. 42. P. 285-311.
  16. Heidenreich E., Novotny R., Kneidinger B et al., 2003. Non-homologous end joinig as an important mutagenic process in cell cycle-arrested cells//EMBO J. Vol. 22. P. 2274-2283.
  17. Inge-Vechtomov S. G., Zhouravleva G. A., Chernoff Y. O., 2007. Biological roles of prion domains//Prion. Vol. 4. P. 228-235.
  18. Johnson A., O'Donnell M., 2005. Cellular DNA replicases: components and dynamics at the replication fork//Annu. Rev. Biochem. Vol. 74 P. 283-315.
  19. Korogodin V. I., Korogodina V. L., Fajszi C et al., 1991. On the dependence of spontaneous mutation rates on the functional state of the genes//Yeast. Vol. 7. P. 105-117.
  20. Kunkel T. A., Burgers P. M., 2008. Dividing the workload at a eukaryotic replication fork//Trends Cell. Biol. Vol. 18. P. 521-527.
  21. Liu V. F., Bhaumik D., Wang T. S., 1999. Mutator phenotype induced by aberrant replication//Mol. Cell. Biol. Vol. 19. P. 1126-1135.
  22. Liu Y., Kao H. I., Bambara R. A., 2004. Flap endonuclease 1: a central component of DNA Metabolism//Ann. Rev. Biochem. Vol. 73. P. 589-615.
  23. Lydeard J. R., Jain S., Yamaguchi M. et al., 2007. Breakinduced replication and telomerase-independent telomere maintenance require Pol32//Nature Vol. 448. P. 820-824.
  24. Lydeard J. R., Lipkin-Moore Z., Sheu Y. J. et al., 2010. Breakinduced replication requires all essential DNA replication factors except those specific for pre-RC assembly//Genes Dev. Vol. 24. P. 1133-144.
  25. Malkova A., Ivavov E. L., Haber J. E., 1996. Double-strand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication//Proc. Natl. Acad. Sci.USA. Vol. 93. P. 7131-7136.
  26. Nick McElhinny S. A., Pavlov Y. I., Kunkel T. A., 2006. Evidence for extrinsic exonucleolytic Proofreading//Cell Cycle Vol. 9. P. 958-962.
  27. Niimi A., Limsirichaikul S., Yoshida S. et al., 2004. Palm mutants in DNA polymerases α and η alter DNA replication fidelity and translesion activity//Mol. Cell. Biol. Vol. 24. P. 2734-2746.
  28. Ogawa M., Limsirichaikul S., Niimi A. et al., 2003. Distinct function of conserved amino acids in the fingers of Saccharomyces cerevisiae DNA polymerase α//J. Biol. Chem. Vol. 278. P. 19071-19078.
  29. Pavlov Y. I., Frahm C., McElhinny S. A et al., 2006-b. Evidence that errors made by DNA polymerase α are corrected by DNA polymerase δ//Curr. Biol. Vol. 16. P. 202-207.
  30. Pavlov Y. I., Newlon C. S., Kunkel T. A., 2002. Yeast origins establish a strand bias for replicational mutagenesis//Mol. Cell. Vol. 10. P. 207-213.
  31. Pavlov Y. I., Shcherbakova P. V., 2010. DNA polymerases at the eukaryotic fork-20 years later//Mutat. Res. Vol. 685. P. 45-53.
  32. Pavlov Y. I., Shcherbakova P. V., Rogozin I. B. et al., 2006-a. Roles of DNA polymerases in replication, repair, and recombination in eukaryotes//Int. Rev. Cytol. Vol. 255. P. 41-132.
  33. Prelich G., 1999. Suppression mechanisms, themes for variation//Trends in Genetics. Vol. 15. P. 261-266.
  34. Rogozin I. B., Pavlov Y. I., Bebenek K. et al., 2001. Somatic mutation hotspots correlate with DNA polymerase η error spectrum//Nat. Immunol. Vol. 2. P. 530-536.
  35. Rojas Gil A. P., Vondrejs V., 1999. Development of papillae on colonies of two isopolyauxotrophic strains of Saccharomyces cerevisiae allelic in RAD6 during adenine starvation//Folia Microbiol. Vol. 44. P. 299-305.
  36. Rosche W. A., Foster P. L., 2000. Determining mutation rates in bacterial populations//Methods. Vol. 20. P. 4-17.
  37. Serio T. R., Lindquist S. L., 1999. [PSI+]: an epigenetic modulator of translation termination Efficiency//Ann. Rev. Cell. Dev. Biol. Vol. 15. P. 661-703.
  38. Steele D. F., Jinks-Robertson S., 1992. An examination of adaptive reversion in Saccharomyces cerevisiae//Genetics. Vol. 132. P. 9-21.
  39. Suzuki M., Niimi A., Limsirichaikul S. et al., 2009. PCNA monoubiquitination and activation of translesion DNA polymerases by DNA polymerase {alpha}//J. Biochem. Vol. 146. P. 13-21.
  40. Waga S., Stillman B., 1998. The DNA replication fork in eukaryotic cells//Ann. Rev. Biochem. Vol. 67. P. 721-751.

Statistics

Views

Abstract - 484

PDF (Russian) - 247

Cited-By


PlumX


Copyright (c) 2011 Babudri N., Achilli A., Martinelli C., Moore E., Lancioni H., Pavlov Y.I.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies