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 Mahajan, K. N.
Right arrow Articles by Ramsden, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mahajan, K. N.
Right arrow Articles by Ramsden, D. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2002, p. 5194-5202, Vol. 22, No. 14
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.14.5194-5202.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Association of DNA Polymerase µ (pol µ) with Ku and Ligase IV: Role for pol µ in End-Joining Double-Strand Break Repair

Kiran N. Mahajan,1 Stephanie A. Nick McElhinny,1,2 Beverly S. Mitchell,1,3,4,5 and Dale A. Ramsden1,2,3*

Lineberger Comprehensive Cancer Center,1 Department of Biochemistry and Biophysics,2 Curriculum in Genetics and Molecular Biology,3 Departments of Pharmacology,4 Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina5

Received 8 October 2001/ Returned for modification 15 November 2001/ Accepted 8 April 2002

Mammalian DNA polymerase µ (pol µ) is related to terminal deoxynucleotidyl transferase, but its biological role is not yet clear. We show here that after exposure of cells to ionizing radiation (IR), levels of pol µ protein increase. pol µ also forms discrete nuclear foci after IR, and these foci are largely coincident with IR-induced foci of {gamma}H2AX, a previously characterized marker of sites of DNA double-strand breaks. pol µ is thus part of the cellular response to DNA double-strand breaks. pol µ also associates in cell extracts with the nonhomologous end-joining repair factor Ku and requires both Ku and another end-joining factor, XRCC4-ligase IV, to form a stable complex on DNA in vitro. pol µ in turn facilitates both stable recruitment of XRCC4-ligase IV to Ku-bound DNA and ligase IV-dependent end joining. In contrast, the related mammalian DNA polymerase ß does not form a complex with Ku and XRCC4-ligase IV and is less effective than pol µ in facilitating joining mediated by these factors. Our data thus support an important role for pol µ in the end-joining pathway for repair of double-strand breaks.

* Corresponding author. Mailing address: Rm. 32-044, Lineberger Comprehensive Cancer Center, Campus Box 7295, Mason Farm Road, 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, July 2002, p. 5194-5202, Vol. 22, No. 14
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.14.5194-5202.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Andrade, P., Martin, M. J., Juarez, R., Lopez de Saro, F., Blanco, L. (2009). Limited terminal transferase in human DNA polymerase {micro} defines the required balance between accuracy and efficiency in NHEJ. Proc. Natl. Acad. Sci. USA 106: 16203-16208 [Abstract] [Full Text]  
  • Covo, S., de Villartay, J.-P., Jeggo, P. A., Livneh, Z. (2009). Translesion DNA synthesis-assisted non-homologous end-joining of complex double-strand breaks prevents loss of DNA sequences in mammalian cells. Nucleic Acids Res 0: gkp703v1-gkp703 [Abstract] [Full Text]  
  • Akopiants, K., Zhou, R.-Z., Mohapatra, S., Valerie, K., Lees-Miller, S. P., Lee, K.-J., Chen, D. J., Revy, P., de Villartay, J.-P., Povirk, L. F. (2009). Requirement for XLF/Cernunnos in alignment-based gap filling by DNA polymerases {lambda} and {micro} for nonhomologous end joining in human whole-cell extracts. Nucleic Acids Res 37: 4055-4062 [Abstract] [Full Text]  
  • Gozalbo-Lopez, B., Andrade, P., Terrados, G., de Andres, B., Serrano, N., Cortegano, I., Palacios, B., Bernad, A., Blanco, L., Marcos, M. A. R., Gaspar, M. L. (2009). A Role for DNA Polymerase {micro} in the Emerging DJH Rearrangements of the Postgastrulation Mouse Embryo. Mol. Cell. Biol. 29: 1266-1275 [Abstract] [Full Text]  
  • Schenten, D., Kracker, S., Esposito, G., Franco, S., Klein, U., Murphy, M., Alt, F. W., Rajewsky, K. (2009). Pol{zeta} ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability. JEM 206: 477-490 [Abstract] [Full Text]  
  • Banos, B., Lazaro, J. M., Villar, L., Salas, M., de Vega, M. (2008). Editing of misaligned 3'-termini by an intrinsic 3'-5' exonuclease activity residing in the PHP domain of a family X DNA polymerase. Nucleic Acids Res 36: 5736-5749 [Abstract] [Full Text]  
  • Lieber, M. R., Raghavan, S. C., Yu, K. (2008). Mechanistic Aspects of Lymphoid Chromosomal Translocations. J Natl Cancer Inst Monogr 2008: 8-11 [Abstract] [Full Text]  
  • Zhou, R.-Z., Blanco, L., Garcia-Diaz, M., Bebenek, K., Kunkel, T. A., Povirk, L. F. (2008). Tolerance for 8-oxoguanine but not thymine glycol in alignment-based gap filling of partially complementary double-strand break ends by DNA polymerase {lambda} in human nuclear extracts. Nucleic Acids Res 36: 2895-2905 [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]  
  • Schild-Poulter, C., Su, A., Shih, A., Kelly, O. P., Fritzler, M. J., Goldstein, R., Hache, R. J. G. (2008). Association of autoantibodies with Ku and DNA repair proteins in connective tissue diseases. Rheumatology (Oxford) 47: 165-171 [Abstract] [Full Text]  
  • Lieber, M. R. (2008). The Mechanism of Human Nonhomologous DNA End Joining. J. Biol. Chem. 283: 1-5 [Abstract] [Full Text]  
  • Capp, J.-P., Boudsocq, F., Besnard, A.-G., Lopez, B. S., Cazaux, C., Hoffmann, J.-S., Canitrot, Y. (2007). Involvement of DNA polymerase {micro} in the repair of a specific subset of DNA double-strand breaks in mammalian cells. Nucleic Acids Res 35: 3551-3560 [Abstract] [Full Text]  
  • Kuhfittig-Kulle, S., Feldmann, E., Odersky, A., Kuliczkowska, A., Goedecke, W., Eggert, A., Pfeiffer, P. (2007). The mutagenic potential of non-homologous end joining in the absence of the NHEJ core factors Ku70/80, DNA-PKcs and XRCC4-LigIV. Mutagenesis 22: 217-233 [Abstract] [Full Text]  
  • Budman, J., Kim, S. A., Chu, G. (2007). Processing of DNA for Nonhomologous End-joining Is Controlled by Kinase Activity and XRCC4/Ligase IV. J. Biol. Chem. 282: 11950-11959 [Abstract] [Full Text]  
  • Roberts, S. A., Ramsden, D. A. (2007). Loading of the Nonhomologous End Joining Factor, Ku, on Protein-occluded DNA Ends. J. Biol. Chem. 282: 10605-10613 [Abstract] [Full Text]  
  • Hentges, P., Ahnesorg, P., Pitcher, R. S., Bruce, C. K., Kysela, B., Green, A. J., Bianchi, J., Wilson, T. E., Jackson, S. P., Doherty, A. J. (2006). Evolutionary and Functional Conservation of the DNA Non-homologous End-joining Protein, XLF/Cernunnos. J. Biol. Chem. 281: 37517-37526 [Abstract] [Full Text]  
  • Juarez, R., Ruiz, J. F., McElhinny, S. A. N., Ramsden, D., Blanco, L. (2006). A specific loop in human DNA polymerase mu allows switching between creative and DNA-instructed synthesis. Nucleic Acids Res 34: 4572-4582 [Abstract] [Full Text]  
  • Pardo, B., Ma, E., Marcand, S. (2006). Mismatch Tolerance by DNA Polymerase Pol4 in the Course of Nonhomologous End Joining in Saccharomyces cerevisiae. Genetics 172: 2689-2694 [Abstract] [Full Text]  
  • Fujisaki, S., Sato, A., Toyomoto, T., Hayano, T., Sugai, M., Kubota, T., Koiwai, O. (2006). Direct binding of TReP-132 with TdT results in reduction of TdT activity. GENES CELLS 11: 47-57 [Abstract] [Full Text]  
  • Jones, K. R., Gewirtz, D. A., Yannone, S. M., Zhou, S., Schatz, D. G., Valerie, K., Povirk, L. F. (2005). Radiosensitization of MDA-MB-231 breast tumor cells by adenovirus-mediated overexpression of a fragment of the XRCC4 protein. Molecular Cancer Therapeutics 4: 1541-1547 [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]  
  • Locatelli, G. A., Di Santo, R., Crespan, E., Costi, R., Roux, A., Hubscher, U., Shevelev, I., Blanca, G., Villani, G., Spadari, S., Maga, G. (2005). Diketo Hexenoic Acid Derivatives Are Novel Selective Non-Nucleoside Inhibitors of Mammalian Terminal Deoxynucleotidyl Transferases, with Potent Cytotoxic Effect against Leukemic Cells. Mol. Pharmacol. 68: 538-550 [Abstract] [Full Text]  
  • Shimazaki, N., Yazaki, T., Kubota, T., Sato, A., Nakamura, A., Kurei, S., Toji, S., Tamai, K., Koiwai, O. (2005). DNA polymerase lambda directly binds to proliferating cell nuclear antigen through its confined C-terminal region. GENES CELLS 10: 705-715 [Abstract] [Full Text]  
  • Dip, R., Naegeli, H. (2005). More than just strand breaks: the recognition of structural DNA discontinuities by DNA-dependent protein kinase catalytic subunit. FASEB J. 19: 704-715 [Abstract] [Full Text]  
  • Daley, J. M., Wilson, T. E. (2005). Rejoining of DNA Double-Strand Breaks as a Function of Overhang Length. Mol. Cell. Biol. 25: 896-906 [Abstract] [Full Text]  
  • McVey, M., Radut, D., Sekelsky, J. J. (2004). End-Joining Repair of Double-Strand Breaks in Drosophila melanogaster Is Largely DNA Ligase IV Independent. Genetics 168: 2067-2076 [Abstract] [Full Text]  
  • Tseng, H.-M., Tomkinson, A. E. (2004). Processing and Joining of DNA Ends Coordinated by Interactions among Dnl4/Lif1, Pol4, and FEN-1. J. Biol. Chem. 279: 47580-47588 [Abstract] [Full Text]  
  • Ruiz, J. F., Lucas, D., Garcia-Palomero, E., Saez, A. I., Gonzalez, M. A., Piris, M. A., Bernad, A., Blanco, L. (2004). Overexpression of human DNA polymerase {micro} (Pol {micro}) in a Burkitt's lymphoma cell line affects the somatic hypermutation rate. Nucleic Acids Res 32: 5861-5873 [Abstract] [Full Text]  
  • Tippin, B., Kobayashi, S., Bertram, J. G., Goodman, M. F. (2004). To Slip or Skip, Visualizing Frameshift Mutation Dynamics for Error-prone DNA Polymerases. J. Biol. Chem. 279: 45360-45368 [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]  
  • Reddy, Y. V. R., Ding, Q., Lees-Miller, S. P., Meek, K., Ramsden, D. A. (2004). Non-homologous End Joining Requires That the DNA-PK Complex Undergo an Autophosphorylation-dependent Rearrangement at DNA Ends. J. Biol. Chem. 279: 39408-39413 [Abstract] [Full Text]  
  • Wang, Y.-G., Nnakwe, C., Lane, W. S., Modesti, M., Frank, K. M. (2004). Phosphorylation and Regulation of DNA Ligase IV Stability by DNA-dependent Protein Kinase. J. Biol. Chem. 279: 37282-37290 [Abstract] [Full Text]  
  • Block, W. D., Yu, Y., Merkle, D., Gifford, J. L., Ding, Q., Meek, K., Lees-Miller, S. P. (2004). Autophosphorylation-dependent remodeling of the DNA-dependent protein kinase catalytic subunit regulates ligation of DNA ends. Nucleic Acids Res 32: 4351-4357 [Abstract] [Full Text]  
  • Repasky, J. A. E., Corbett, E., Boboila, C., Schatz, D. G. (2004). Mutational Analysis of Terminal Deoxynucleotidyltransferase- Mediated N-Nucleotide Addition in V(D)J Recombination. J. Immunol. 172: 5478-5488 [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]  
  • Lee, J. W., Blanco, L., Zhou, T., Garcia-Diaz, M., Bebenek, K., Kunkel, T. A., Wang, Z., Povirk, L. F. (2004). Implication of DNA Polymerase {lambda} in Alignment-based Gap Filling for Nonhomologous DNA End Joining in Human Nuclear Extracts. J. Biol. Chem. 279: 805-811 [Abstract] [Full Text]  
  • Bebenek, K., Garcia-Diaz, M., Blanco, L., Kunkel, T. A. (2003). The Frameshift Infidelity of Human DNA Polymerase {lambda}: IMPLICATIONS FOR FUNCTION. J. Biol. Chem. 278: 34685-34690 [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]  
  • Smith, J., Riballo, E., Kysela, B., Baldeyron, C., Manolis, K., Masson, C., Lieber, M. R., Papadopoulo, D., Jeggo, P. (2003). Impact of DNA ligase IV on the fidelity of end joining in human cells. Nucleic Acids Res 31: 2157-2167 [Abstract] [Full Text]  
  • Nick McElhinny, S. A., Ramsden, D. A. (2003). Polymerase Mu Is a DNA-Directed DNA/RNA Polymerase. Mol. Cell. Biol. 23: 2309-2315 [Abstract] [Full Text]  
  • Shcherbakova, P. V., Bebenek, K., Kunkel, T. A. (2003). Functions of Eukaryotic DNA Polymerases. Sci Aging Knowl Environ 2003: re3-3 [Abstract] [Full Text]  
  • Lee, J. W., Yannone, S. M., Chen, D. J., Povirk, L. F. (2003). Requirement for XRCC4 and DNA Ligase IV in Alignment-based Gap Filling for Nonhomologous DNA End Joining in Vitro. Cancer Res. 63: 22-24 [Abstract] [Full Text]  
  • Tseng, H.-M., Tomkinson, A. E. (2002). A Physical and Functional Interaction between Yeast Pol4 and Dnl4-Lif1 Links DNA Synthesis and Ligation in Nonhomologous End Joining. J. Biol. Chem. 277: 45630-45637 [Abstract] [Full Text]  
  • Zhang, Y., Wu, X., Guo, D., Rechkoblit, O., Taylor, J.-S., Geacintov, N. E., Wang, Z. (2002). Lesion Bypass Activities of Human DNA Polymerase {micro}. J. Biol. Chem. 277: 44582-44587 [Abstract] [Full Text]  
  • Wilson, T. E. (2002). A Genomics-Based Screen for Yeast Mutants With an Altered Recombination/End-Joining Repair Ratio. Genetics 162: 677-688 [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»