This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nick McElhinny, S. A.
Right arrow Articles by Ramsden, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nick McElhinny, S. A.
Right arrow Articles by Ramsden, D. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2003, p. 2309-2315, Vol. 23, No. 7
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.7.2309-2315.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Polymerase Mu Is a DNA-Directed DNA/RNA Polymerase

Stephanie A. Nick McElhinny1,2 and Dale A. Ramsden1,2,3*

Department of Biochemistry and Biophysics,1 Lineberger Comprehensive Cancer Center,2 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina3

Received 11 November 2002/ Returned for modification 18 December 2002/ Accepted 8 January 2003

DNA polymerases are defined as such because they use deoxynucleotides instead of ribonucleotides with high specificity. We show here that polymerase mu (pol µ), implicated in the nonhomologous end-joining pathway for repair of DNA double-strand breaks, incorporates both ribonucleotides and deoxynucleotides in a template-directed manner. pol µ has an approximately 1,000-fold-reduced ability to discriminate against ribonucleotides compared to that of the related pol ß, although pol µ's substrate specificity is similar to that of pol ß in most other respects. Moreover, pol µ more frequently incorporates ribonucleotides when presented with nucleotide concentrations that approximate cellular pools. We therefore addressed the impact of ribonucleotide incorporation on the activities of factors required for double-strand break repair by nonhomologous end joining. We determined that the ligase required for this pathway readily joined strand breaks with terminal ribonucleotides. Most significantly, pol µ frequently introduced ribonucleotides into the repair junctions of an in vitro nonhomologous end-joining reaction, an activity that would be expected to have important consequences in the context of cellular double-strand break repair.

* Corresponding author. Mailing address: Room 32-044, Lineberger Comprehensive Cancer Center, Campus Box 7295, Mason Farm Rd., University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-9839. Fax: (919) 966-3015. E-mail: Dale_Ramsden{at}med.unc.edu.

Molecular and Cellular Biology, April 2003, p. 2309-2315, Vol. 23, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.7.2309-2315.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Romain, F., Barbosa, I., Gouge, J., Rougeon, F., Delarue, M. (2009). Conferring a template-dependent polymerase activity to terminal deoxynucleotidyltransferase by mutations in the Loop1 region. Nucleic Acids Res 37: 4642-4656 [Abstract] [Full Text]  
  • Nakane, S., Nakagawa, N., Kuramitsu, S., Masui, R. (2009). Characterization of DNA polymerase X from Thermus thermophilus HB8 reveals the POLXc and PHP domains are both required for 3'-5' exonuclease activity. Nucleic Acids Res 37: 2037-2052 [Abstract] [Full Text]  
  • Davis, B. J., Havener, J. M., Ramsden, D. A. (2008). End-bridging is required for pol {micro} to efficiently promote repair of noncomplementary ends by nonhomologous end joining. Nucleic Acids Res 36: 3085-3094 [Abstract] [Full Text]  
  • Gu, J., Lieber, M. R. (2008). Mechanistic flexibility as a conserved theme across 3 billion years of nonhomologous DNA end-joining. Genes Dev. 22: 411-415 [Full Text]  
  • Gu, J., Lu, H., Tsai, A. G., Schwarz, K., Lieber, M. R. (2007). Single-stranded DNA ligation and XLF-stimulated incompatible DNA end ligation by the XRCC4-DNA ligase IV complex: influence of terminal DNA sequence. Nucleic Acids Res 35: 5755-5762 [Abstract] [Full Text]  
  • Picher, A. J., Garcia-Diaz, M., Bebenek, K., Pedersen, L. C., Kunkel, T. A., Blanco, L. (2006). Promiscuous mismatch extension by human DNA polymerase lambda. Nucleic Acids Res 34: 3259-3266 [Abstract] [Full Text]  
  • Jackman, J. E., Phizicky, E. M. (2006). tRNAHis guanylyltransferase catalyzes a 3'-5' polymerization reaction that is distinct from G-1 addition. Proc. Natl. Acad. Sci. USA 103: 8640-8645 [Abstract] [Full Text]  
  • Frouin, I., Toueille, M., Ferrari, E., Shevelev, I., Hubscher, U. (2005). Phosphorylation of human DNA polymerase {lambda} by the cyclin-dependent kinase Cdk2/cyclin A complex is modulated by its association with proliferating cell nuclear antigen. Nucleic Acids Res 33: 5354-5361 [Abstract] [Full Text]  
  • Gonzalez-Barrera, S., Sanchez, A., Ruiz, J. F., Juarez, R., Picher, A. J., Terrados, G., Andrade, P., Blanco, L. (2005). Characterization of SpPol4, a unique X-family DNA polymerase in Schizosaccharomyces pombe. Nucleic Acids Res 33: 4762-4774 [Abstract] [Full Text]  
  • Daley, J. M., Laan, R. L. V., Suresh, A., Wilson, T. E. (2005). DNA Joint Dependence of Pol X Family Polymerase Action in Nonhomologous End Joining. J. Biol. Chem. 280: 29030-29037 [Abstract] [Full Text]  
  • Bebenek, K., Garcia-Diaz, M., Patishall, S. R., Kunkel, T. A. (2005). Biochemical Properties of Saccharomyces cerevisiae DNA Polymerase IV. J. Biol. Chem. 280: 20051-20058 [Abstract] [Full Text]  
  • Della, M., Palmbos, P. L., Tseng, H.-M., Tonkin, L. M., Daley, J. M., Topper, L. M., Pitcher, R. S., Tomkinson, A. E., Wilson, T. E., Doherty, A. J. (2004). Mycobacterial Ku and Ligase Proteins Constitute a Two-Component NHEJ Repair Machine. Science 306: 683-685 [Abstract] [Full Text]  
  • Covo, S., Blanco, L., Livneh, Z. (2004). Lesion Bypass by Human DNA Polymerase {micro} Reveals a Template-dependent, Sequence-independent Nucleotidyl Transferase Activity. J. Biol. Chem. 279: 859-865 [Abstract] [Full Text]  
  • Diaz, M., Watson, N. B., Turkington, G., Verkoczy, L. K., Klinman, N. R., McGregor, W. G. (2003). Decreased Frequency and Highly Aberrant Spectrum of Ultraviolet-Induced Mutations in the hprt Gene of Mouse Fibroblasts Expressing Antisense RNA to DNA Polymerase {zeta}. Mol Cancer Res 1: 836-847 [Abstract] [Full Text]  
  • Ruiz, J. F., Juarez, R., Garcia-Diaz, M., Terrados, G., Picher, A. J., Gonzalez-Barrera, S., Fernandez de Henestrosa, A. R., Blanco, L. (2003). Lack of sugar discrimination by human Pol {micro} requires a single glycine residue. Nucleic Acids Res 31: 4441-4449 [Abstract] [Full Text]  
  • Hashimoto, M., Imhoff, B., Ali, M. M., Kow, Y. W. (2003). HU Protein of Escherichia coli Has a Role in the Repair of Closely Opposed Lesions in DNA. J. Biol. Chem. 278: 28501-28507 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»