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 Ma, J.-L.
Right arrow Articles by Lee, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ma, J.-L.
Right arrow Articles by Lee, S. E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2003, p. 8820-8828, Vol. 23, No. 23
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.23.8820-8828.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Yeast Mre11 and Rad1 Proteins Define a Ku-Independent Mechanism To Repair Double-Strand Breaks Lacking Overlapping End Sequences

Jia-Lin Ma,1 Eun Mi Kim,1 James E. Haber,2 and Sang Eun Lee1*

Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245,1 Rosenstiel Center and Department of Biology, Brandeis University, Waltham, Massachusetts 024542

Received 1 August 2003/ Returned for modification 19 August 2003/ Accepted 27 August 2003

End joining of double-strand breaks (DSBs) requires Ku proteins and frequently involves base pairing between complementary terminal sequences. To define the role of terminal base pairing in end joining, two oppositely oriented HO endonuclease cleavage sites separated by 2.0 kb were integrated into yeast chromosome III, where constitutive expression of HO endonuclease creates two simultaneous DSBs with no complementary end sequence. Lack of complementary sequence in their 3' single-strand overhangs facilitates efficient repair events distinctly different from when the 3' ends have a 4-bp sequence base paired in various ways to create 2- to 3-bp insertions. Repair of noncomplementary ends results in a set of nonrandom deletions of up to 302 bp, annealed by imperfect microhomology of about 8 to 10 bp at the junctions. This microhomology-mediated end joining (MMEJ) is Ku independent, but strongly dependent on Mre11, Rad50, and Rad1 proteins and partially dependent on Dnl4 protein. The MMEJ also occurs when Rad52 is absent, but the extent of deletions becomes more limited. The increased gamma ray sensitivity of rad1{Delta} rad52{Delta} yku70{Delta} strains compared to rad52{Delta} yku70{Delta} strains suggests that MMEJ also contributes to the repair of DSBs induced by ionizing radiation.

* Corresponding author. Mailing address: Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, 15355 Lambda Dr., San Antonio, TX 78245. Phone: (210) 567-7273. Fax: (210) 567-7269. E-mail: lees4{at}uthscsa.edu.

Molecular and Cellular Biology, December 2003, p. 8820-8828, Vol. 23, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.23.8820-8828.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Taylor, E. M., Cecillon, S. M., Bonis, A., Chapman, J. R., Povirk, L. F., Lindsay, H. D. (2009). The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis. Nucleic Acids Res 0: gkp905v1-gkp905 [Abstract] [Full Text]  
  • Zhuang, J., Jiang, G., Willers, H., Xia, F. (2009). Exonuclease Function of Human Mre11 Promotes Deletional Nonhomologous End Joining. J. Biol. Chem. 284: 30565-30573 [Abstract] [Full Text]  
  • Moore, D. M., Karlin, J., Gonzalez-Barrera, S., Mardiros, A., Lisby, M., Doughty, A., Gilley, J., Rothstein, R., Friedberg, E. C., Fischhaber, P. L. (2009). Rad10 exhibits lesion-dependent genetic requirements for recruitment to DNA double-strand breaks in Saccharomyces cerevisiae. Nucleic Acids Res 37: 6429-6438 [Abstract] [Full Text]  
  • Grandin, N., Charbonneau, M. (2009). Telomerase- and Rad52-Independent Immortalization of Budding Yeast by an Inherited-Long-Telomere Pathway of Telomeric Repeat Amplification. Mol. Cell. Biol. 29: 965-985 [Abstract] [Full Text]  
  • Lowden, M. R., Meier, B., Lee, T. W.-s., Hall, J., Ahmed, S. (2008). End Joining at Caenorhabditis elegans Telomeres. Genetics 180: 741-754 [Abstract] [Full Text]  
  • Ahmad, A., Robinson, A. R., Duensing, A., van Drunen, E., Beverloo, H. B., Weisberg, D. B., Hasty, P., Hoeijmakers, J. H. J., Niedernhofer, L. J. (2008). ERCC1-XPF Endonuclease Facilitates DNA Double-Strand Break Repair. Mol. Cell. Biol. 28: 5082-5092 [Abstract] [Full Text]  
  • Mansour, W. Y., Schumacher, S., Rosskopf, R., Rhein, T., Schmidt-Petersen, F., Gatzemeier, F., Haag, F., Borgmann, K., Willers, H., Dahm-Daphi, J. (2008). Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks. Nucleic Acids Res 36: 4088-4098 [Abstract] [Full Text]  
  • Schulte-Uentrop, L., El-Awady, R. A., Schliecker, L., Willers, H., Dahm-Daphi, J. (2008). Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks. Nucleic Acids Res 36: 2561-2569 [Abstract] [Full Text]  
  • Haber, J. E. (2008). Alternative endings. Proc. Natl. Acad. Sci. USA 105: 405-406 [Full Text]  
  • Lieber, M. R. (2008). The Mechanism of Human Nonhomologous DNA End Joining. J. Biol. Chem. 283: 1-5 [Abstract] [Full Text]  
  • Guirouilh-Barbat, J., Rass, E., Plo, I., Bertrand, P., Lopez, B. S. (2007). Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends. Proc. Natl. Acad. Sci. USA 104: 20902-20907 [Abstract] [Full Text]  
  • Inagaki, K., Lewis, S. M., Wu, X., Ma, C., Munroe, D. J., Fuess, S., Storm, T. A., Kay, M. A., Nakai, H. (2007). DNA Palindromes with a Modest Arm Length of {gtrsim}20 Base Pairs Are a Significant Target for Recombinant Adeno-Associated Virus Vector Integration in the Liver, Muscles, and Heart in Mice. J. Virol. 81: 11290-11303 [Abstract] [Full Text]  
  • Heacock, M. L., Idol, R. A., Friesner, J. D., Britt, A. B., Shippen, D. E. (2007). Telomere dynamics and fusion of critically shortened telomeres in plants lacking DNA ligase IV. Nucleic Acids Res 35: 6490-6500 [Abstract] [Full Text]  
  • Capper, R., Britt-Compton, B., Tankimanova, M., Rowson, J., Letsolo, B., Man, S., Haughton, M., Baird, D. M. (2007). The nature of telomere fusion and a definition of the critical telomere length in human cells. Genes Dev. 21: 2495-2508 [Abstract] [Full Text]  
  • Burton, P., McBride, D. J., Wilkes, J. M., Barry, J. D., McCulloch, R. (2007). Ku Heterodimer-Independent End Joining in Trypanosoma brucei Cell Extracts Relies upon Sequence Microhomology. Eukaryot Cell 6: 1773-1781 [Abstract] [Full Text]  
  • Pike, B. L., Heierhorst, J. (2007). Mdt1 Facilitates Efficient Repair of Blocked DNA Double-Strand Breaks and Recombinational Maintenance of Telomeres. Mol. Cell. Biol. 27: 6532-6545 [Abstract] [Full Text]  
  • Haviv-Chesner, A., Kobayashi, Y., Gabriel, A., Kupiec, M. (2007). Capture of linear fragments at a double-strand break in yeast. Nucleic Acids Res 0: gkm521v1-11 [Abstract] [Full Text]  
  • Chan, C. Y., Kiechle, M., Manivasakam, P., Schiestl, R. H. (2007). Ionizing radiation and restriction enzymes induce microhomology-mediated illegitimate recombination in Saccharomyces cerevisiae. Nucleic Acids Res 35: 5051-5059 [Abstract] [Full Text]  
  • Lee, K., Lee, S. E. (2007). Saccharomyces cerevisiae Sae2- and Tel1-Dependent Single-Strand DNA Formation at DNA Break Promotes Microhomology-Mediated End Joining. Genetics 176: 2003-2014 [Abstract] [Full Text]  
  • Ueno, K., Uno, J., Nakayama, H., Sasamoto, K., Mikami, Y., Chibana, H. (2007). Development of a Highly Efficient Gene Targeting System Induced by Transient Repression of YKU80 Expression in Candida glabrata. Eukaryot Cell 6: 1239-1247 [Abstract] [Full Text]  
  • Decottignies, A. (2007). Microhomology-Mediated End Joining in Fission Yeast Is Repressed by Pku70 and Relies on Genes Involved in Homologous Recombination. Genetics 176: 1403-1415 [Abstract] [Full Text]  
  • Ishibashi, K., Suzuki, K., Ando, Y., Takakura, C., Inoue, H. (2006). Nonhomologous chromosomal integration of foreign DNA is completely dependent on MUS-53 (human Lig4 homolog) in Neurospora. Proc. Natl. Acad. Sci. USA 103: 14871-14876 [Abstract] [Full Text]  
  • Harris, J., Lowden, M., Clejan, I., Tzoneva, M., Thomas, J. H., Hodgkin, J., Ahmed, S. (2006). Mutator Phenotype of Caenorhabditis elegans DNA Damage Checkpoint Mutants. Genetics 174: 601-616 [Abstract] [Full Text]  
  • Clejan, I., Boerckel, J., Ahmed, S. (2006). Developmental Modulation of Nonhomologous End Joining in Caenorhabditis elegans. Genetics 173: 1301-1317 [Abstract] [Full Text]  
  • Malik, M., Nitiss, K. C., Enriquez-Rios, V., Nitiss, J. L. (2006). Roles of nonhomologous end-joining pathways in surviving topoisomerase II-mediated DNA damage.. Molecular Cancer Therapeutics 5: 1405-1414 [Abstract] [Full Text]  
  • Beumer, K., Bhattacharyya, G., Bibikova, M., Trautman, J. K., Carroll, D. (2006). Efficient Gene Targeting in Drosophila With Zinc-Finger Nucleases. Genetics 172: 2391-2403 [Abstract] [Full Text]  
  • Zhuang, J., Zhang, J., Willers, H., Wang, H., Chung, J. H., van Gent, D. C., Hallahan, D. E., Powell, S. N., Xia, F. (2006). Checkpoint Kinase 2-Mediated Phosphorylation of BRCA1 Regulates the Fidelity of Nonhomologous End-Joining. Cancer Res. 66: 1401-1408 [Abstract] [Full Text]  
  • Sterling, C. H., Sweasy, J. B. (2006). DNA Polymerase 4 of Saccharomyces cerevisiae Is Important for Accurate Repair of Methyl-Methanesulfonate-Induced DNA Damage. Genetics 172: 89-98 [Abstract] [Full Text]  
  • Palmbos, P. L., Daley, J. M., Wilson, T. E. (2005). Mutations of the Yku80 C Terminus and Xrs2 FHA Domain Specifically Block Yeast Nonhomologous End Joining. Mol. Cell. Biol. 25: 10782-10790 [Abstract] [Full Text]  
  • Decottignies, A. (2005). Capture of Extranuclear DNA at Fission Yeast Double-Strand Breaks. Genetics 171: 1535-1548 [Abstract] [Full Text]  
  • Larijani, M., Zaheen, A., Frieder, D., Wang, Y., Wu, G. E., Edelmann, W., Martin, A. (2005). Lack of MSH2 involvement differentiates V(D)J recombination from other non-homologous end joining events. Nucleic Acids Res 33: 6733-6742 [Abstract] [Full Text]  
  • Chen, S., Davies, A. A., Sagan, D., Ulrich, H. D. (2005). The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner. Nucleic Acids Res 33: 5878-5886 [Abstract] [Full Text]  
  • Zhang, J., Powell, S. N. (2005). The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair. Mol Cancer Res 3: 531-539 [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]  
  • Hwang, J.-Y., Smith, S., Myung, K. (2005). The Rad1-Rad10 Complex Promotes the Production of Gross Chromosomal Rearrangements From Spontaneous DNA Damage in Saccharomyces cerevisiae. Genetics 169: 1927-1937 [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]  
  • Romeijn, R. J., Gorski, M. M., van Schie, M. A., Noordermeer, J. N., Mullenders, L. H., Ferro, W., Pastink, A. (2005). Lig4 and Rad54 Are Required for Repair of DNA Double-Strand Breaks Induced by P-Element Excision in Drosophila. Genetics 169: 795-806 [Abstract] [Full Text]  
  • Pan-Hammarstrom, Q., Jones, A.-M., Lahdesmaki, A., Zhou, W., Gatti, R. A., Hammarstrom, L., Gennery, A. R., Ehrenstein, M. R. (2005). Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells. JEM 201: 189-194 [Abstract] [Full Text]  
  • Tsuji, H., Ishii-Ohba, H., Katsube, T., Ukai, H., Aizawa, S., Doi, M., Hioki, K., Ogiu, T. (2004). Involvement of Illegitimate V(D)J Recombination or Microhomology-Mediated Nonhomologous End-Joining in the Formation of Intragenic Deletions of the Notch1 Gene in Mouse Thymic Lymphomas. Cancer Res. 64: 8882-8890 [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]  
  • Bentley, J., Diggle, C. P., Harnden, P., Knowles, M. A., Kiltie, A. E. (2004). DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining. Nucleic Acids Res 32: 5249-5259 [Abstract] [Full Text]  
  • Puizina, J., Siroky, J., Mokros, P., Schweizer, D., Riha, K. (2004). Mre11 Deficiency in Arabidopsis Is Associated with Chromosomal Instability in Somatic Cells and Spo11-Dependent Genome Fragmentation during Meiosis. Plant Cell 16: 1968-1978 [Abstract] [Full Text]  
  • Nakamura, T. M., Du, L.-L., Redon, C., Russell, P. (2004). Histone H2A Phosphorylation Controls Crb2 Recruitment at DNA Breaks, Maintains Checkpoint Arrest, and Influences DNA Repair in Fission Yeast. Mol. Cell. Biol. 24: 6215-6230 [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»