This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harrington, J Articles by Lieber, M R Search for Related Content PubMed PubMed Citation Articles by Harrington, J Articles by Lieber, M R

 Previous Article  |  Next Article 

Mol Cell Biol. 1992 October; 12(10): 4758-4768

Analysis of the defect in DNA end joining in the murine scid mutation.

Department of Pathology, Stanford University School of Medicine, California 94305-5324.

ABSTRACT

Murine severe combined immune deficiency (scid) is marked by a 5,000-fold reduction in coding joint formation in V(D)J recombination of antigen receptors. Others have demonstrated a sensitivity to double-strand breaks generated by ionizing radiation and bleomycin. We were interested in establishing the extent of the defect in intramolecular and intermolecular DNA end joining in lymphoid and nonlymphoid cells from scid mice. We conducted a series of studies probing the ability of these cells to resolve free ends of linear DNA molecules having various biochemical end configurations. We find that the stable integration of linear DNA into scid fibroblasts is reduced 11- to 75-fold compared with that in normal fibroblasts. In contrast, intramolecular and intermolecular end joining occur at normal frequencies in scid lymphocytes and fibroblasts. This normal level of end joining is observed regardless of the type of overhang and regardless of the requirement for nucleolytic activities prior to ligation. The fact that free ends having a wide variety of end configurations are recircularized normally in scid cells rules out certain models for the defect in scid. We discuss the types of DNA end joining reactions that are and are not affected in this double-strand break repair defect in the context of a hairpin model for V(D)J recombination.

This article has been cited by other articles:

• Rosidi, B., Wang, M., Wu, W., Sharma, A., Wang, H., Iliakis, G. (2008). Histone H1 functions as a stimulatory factor in backup pathways of NHEJ. Nucleic Acids Res 36: 1610-1623 [Abstract] [Full Text]  
• Kiefer, K., Oshinsky, J., Kim, J., Nakajima, P. B., Bosma, G. C., Bosma, M. J. (2007). The catalytic subunit of DNA-protein kinase (DNA-PKcs) is not required for Ig class-switch recombination. Proc. Natl. Acad. Sci. USA 104: 2843-2848 [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]  
• Wang, H., Rosidi, B., Perrault, R., Wang, M., Zhang, L., Windhofer, F., Iliakis, G. (2005). DNA Ligase III as a Candidate Component of Backup Pathways of Nonhomologous End Joining. Cancer Res. 65: 4020-4030 [Abstract] [Full Text]  
• Lou, Z., Chen, B. P.-C., Asaithamby, A., Minter-Dykhouse, K., Chen, D. J., Chen, J. (2004). MDC1 Regulates DNA-PK Autophosphorylation in Response to DNA Damage. J. Biol. Chem. 279: 46359-46362 [Abstract] [Full Text]  
• Zhang, J., Willers, H., Feng, Z., Ghosh, J. C., Kim, S., Weaver, D. T., Chung, J. H., Powell, S. N., Xia, F. (2004). Chk2 Phosphorylation of BRCA1 Regulates DNA Double-Strand Break Repair. Mol. Cell. Biol. 24: 708-718 [Abstract] [Full Text]  
• Wang, H., Perrault, A. R., Takeda, Y., Qin, W., Wang, H., Iliakis, G. (2003). Biochemical evidence for Ku-independent backup pathways of NHEJ. Nucleic Acids Res 31: 5377-5388 [Abstract] [Full Text]  
• Bosma, G. C., Kim, J., Urich, T., Fath, D. M., Cotticelli, M. G., Ruetsch, N. R., Radic, M. Z., Bosma, M. J. (2002). DNA-dependent Protein Kinase Activity Is Not Required for Immunoglobulin Class Switching. J. Exp. Med. 196: 1483-1495 [Abstract] [Full Text]  
• Nakajima, P. B., Bosma, M. J. (2002). Variable Diversity Joining Recombination: Nonhairpin Coding Ends in Thymocytes of SCID and Wild-Type Mice. J. Immunol. 169: 3094-3104 [Abstract] [Full Text]  
• Binnie, A., Olson, S., Wu, G. E., Lewis, S. M. (1999). Gamma-Irradiation Directly Affects the Formation of Coding Joints in SCID Cell Lines. J. Immunol. 163: 5418-5426 [Abstract] [Full Text]  
• Liu, L., Kwak, Y.-T., Bex, F., García-Martínez, L. F., Li, X.-H., Meek, K., Lane, W. S., Gaynor, R. B. (1998). DNA-Dependent Protein Kinase Phosphorylation of Ikappa Balpha and Ikappa Bbeta Regulates NF-kappa B DNA Binding Properties. Mol. Cell. Biol. 18: 4221-4234 [Abstract] [Full Text]  
• Liang, F., Jasin, M. (1996). Ku80-deficient Cells Exhibit Excess Degradation of Extrachromosomal DNA. J. Biol. Chem. 271: 14405-14411 [Abstract] [Full Text]  
• Jessberger, R., Riwar, B., Rolink, A., Rodewald, H.-R. (1995). Stimulation of Defective DNA Transfer Activity in Recombination Deficient SCID Cell Extracts by a 72-kDa Protein from Wild-type Thymocytes. J. Biol. Chem. 270: 6788-6797 [Abstract] [Full Text]  
• Danska, J., Pflumio, F, Williams, C., Huner, O, Dick, J., Guidos, C. (1994). Rescue of T cell-specific V(D)J recombination in SCID mice by DNA-damaging agents. Science 266: 450-455 [Abstract]