A Role for DNA Polymerase μ in the Emerging DJ_H Rearrangements of the Postgastrulation Mouse Embryo

REFERENCES

• Alt, F. W., T. K. Blackwell, and G. D. Yancopoulos. 1987. Development of the primary antibody repertoire. Science 238:1079–1087.
   PubMed Web of Science ®Google Scholar
• Baba, Y., R. Pelayo, and P. W. Kincade. 2004. Relationships between hematopoietic stem cells and lymphocyte progenitors. Trends Immunol. 25:645–649.
   PubMedGoogle Scholar
• Bentolila, L. A., S. Olson, A. Marshall, F. Rougeon, C. J. Paige, N. Doyen, and G. E. Wu. 1999. Extensive junctional diversity in Ig light chain genes from early B cell progenitors of mu MT mice. J. Immunol. 162:2123–2128.
   PubMedGoogle Scholar
• Bertocci, B., A. De Smet, C. Berek, J. C. Weill, and C. A. Reynaud. 2003. Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu. Immunity 19:203–211.
   PubMedGoogle Scholar
• Bertocci, B., A. De Smet, J. C. Weill, and C. A. Reynaud. 2006. Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J. recombination in vivo. Immunity 25:31–41.
   PubMed Web of Science ®Google Scholar
• Bertrand, J. Y., A. Jalil, M. Klaine, S. Jung, A. Cumano, and I. Godin. 2005. Three pathways to mature macrophages in the early mouse yolk sac. Blood 106:3004–3011.
   PubMedGoogle Scholar
• Bogue, M., S. Candeias, C. Benoist, and D. Mathis. 1991. A special repertoire of alpha:beta T cells in neonatal mice. EMBO J. 10:3647–3654.
   PubMedGoogle Scholar
• Bogue, M., S. Gilfillan, C. Benoist, and D. Mathis. 1992. Regulation of N-region diversity in antigen receptors through thymocyte differentiation and thymus ontogeny. Proc. Natl. Acad. Sci. USA 89:11011–11015.
   PubMed Web of Science ®Google Scholar
• Capp, J. P., F. Boudsocq, A. G. Besnard, B. S. Lopez, C. Cazaux, J. S. Hoffmann, and Y. Canitrot. 2007. Involvement of DNA polymerase mu in the repair of a specific subset of DNA double-strand breaks in mammalian cells. Nucleic Acids Res. 35:3551–3560.
   PubMedGoogle Scholar
• Carey, J. B., C. S. Moffatt-Blue, L. C. Watson, A. L. Gavin, and A. J. Feeney. 2008. Repertoire-based selection into the marginal zone compartment during B cell development. J. Exp. Med. 205:2043–2052.
   PubMedGoogle Scholar
• Carlsson, L., C. Overmo, and D. Holmberg. 1992. Selection against N-region diversity in immunoglobulin heavy chain variable regions during the development of pre-immune B cell repertoires. Int. Immunol. 4:549–553.
   PubMedGoogle Scholar
• Cassady-Cain, R. L., and A. K. Kaushik. 2006. Increased negative selection impairs neonatal B cell repertoire but does not directly lead to generation of disease-associated IgM auto-antibodies. Int. Immunol. 18:661–669.
   PubMedGoogle Scholar
• Ceredig, R., E. ten Boekel, A. Rolink, F. Melchers, and J. Andersson. 1998. Fetal liver organ cultures allow the proliferative expansion of pre-B receptor-expressing pre-B-II cells and the differentiation of immature and mature B cells in vitro. Int. Immunol. 10:49–59.
   PubMedGoogle Scholar
• Chang, Y., C. J. Paige, and G. E. Wu. 1992. Enumeration and characterization of DJH structures in mouse fetal liver. EMBO J. 11:1891–1899.
   PubMedGoogle Scholar
• Corneo, B., R. L. Wendland, L. Deriano, X. Cui, I. A. Klein, S. Y. Wong, S. Arnal, A. J. Holub, G. R. Weller, B. A. Pancake, S. Shah, V. L. Brandt, K. Meek, and D. B. Roth. 2007. Rag mutations reveal robust alternative end joining. Nature 449:483–486.
   PubMed Web of Science ®Google Scholar
• Covo, S., L. Blanco, and Z. Livneh. 2004. Lesion bypass by human DNA polymerase mu reveals a template-dependent, sequence-independent nucleotidyl transferase activity. J. Biol. Chem. 279:859–865.
   PubMedGoogle Scholar
• Davis, B. J., J. M. Havener, and D. A. Ramsden. 2008. End-bridging is required for polμ to efficiently promote repair of noncomplementary ends by nonhomologous end joining. Nucleic Acids Res. 36:3085–3094.
   PubMed Web of Science ®Google Scholar
• de Andres, B., I. Cortegano, N. Serrano, B. del Rio, P. Martin, P. Gonzalo, M. A. Marcos, and M. L. Gaspar. 2007. A population of CD19highCD45R−/lowCD21low B lymphocytes poised for spontaneous secretion of IgG and IgA antibodies. J. Immunol. 179:5326–5334.
   PubMedGoogle Scholar
• de Andres, B., P. Gonzalo, S. Minguet, J. A. Martinez-Marin, P. G. Soro, M. A. Marcos, and M. L. Gaspar. 2002. The first 3 days of B-cell development in the mouse embryo. Blood 100:4074–4081.
   PubMedGoogle Scholar
• Delarue, M., J. B. Boule, J. Lescar, N. Expert-Bezancon, N. Jourdan, N. Sukumar, F. Rougeon, and C. Papanicolaou. 2002. Crystal structures of a template-independent DNA polymerase: murine terminal deoxynucleotidyltransferase. EMBO J. 21:427–439.
   PubMed Web of Science ®Google Scholar
• Delassus, S., S. Darche, P. Kourilsky, and A. Cumano. 1998. Ontogeny of the heavy chain immunoglobulin repertoire in fetal liver and bone marrow. J. Immunol. 160:3274–3280.
   PubMedGoogle Scholar
• Dominguez, O., J. F. Ruiz, T. Lain de Lera, M. Garcia-Diaz, M. A. Gonzalez, T. Kirchhoff, A. C. Martinez, A. Bernad, and L. Blanco. 2000. DNA polymerase mu (Pol mu), homologous to TdT, could act as a DNA mutator in eukaryotic cells. EMBO J. 19:1731–1742.
   PubMed Web of Science ®Google Scholar
• Egawa, T., K. Kawabata, H. Kawamoto, K. Amada, R. Okamoto, N. Fujii, T. Kishimoto, Y. Katsura, and T. Nagasawa. 2001. The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor. Immunity 15:323–334.
   PubMed Web of Science ®Google Scholar
• Ezekiel, U. R., T. Sun, G. Bozek, and U. Storb. 1997. The composition of coding joints formed in V(D)J recombination is strongly affected by the nucleotide sequence of the coding ends and their relationship to the recombination signal sequences. Mol. Cell. Biol. 17:4191–4197.
   PubMedGoogle Scholar
• Fang, W., D. L. Mueller, C. A. Pennell, J. J. Rivard, Y. S. Li, R. R. Hardy, M. S. Schlissel, and T. W. Behrens. 1996. Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-xL transgene. Immunity 4:291–299.
   PubMedGoogle Scholar
• Fazilleau, N., J. P. Cabaniols, F. Lemaitre, I. Motta, P. Kourilsky, and J. M. Kanellopoulos. 2005. Vα and Vβ public repertoires are highly conserved in terminal deoxynucleotidyl transferase-deficient mice. J. Immunol. 174:345–355.
   PubMedGoogle Scholar
• Feeney, A. J. 1990. Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J. junctional sequences. J. Exp. Med. 172:1377–1390.
   PubMedGoogle Scholar
• Feeney, A. J. 1992. Predominance of VH-D-JH junctions occurring at sites of short sequence homology results in limited junctional diversity in neonatal antibodies. J. Immunol. 149:222–229.
   PubMedGoogle Scholar
• Gerstein, R. M., and M. R. Lieber. 1993. Coding end sequence can markedly affect the initiation of V(D)J. recombination. Genes Dev. 7:1459–1469.
   PubMedGoogle Scholar
• Gilfillan, S., A. Dierich, M. Lemeur, C. Benoist, and D. Mathis. 1993. Mice lacking TdT: mature animals with an immature lymphocyte repertoire. Science 261:1175–1178.
   PubMed Web of Science ®Google Scholar
• Godin, I. E., J. A. Garcia-Porrero, A. Coutinho, F. Dieterlen-Lievre, and M. A. Marcos. 1993. Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors. Nature 364:67–70.
   PubMed Web of Science ®Google Scholar
• Gu, H., I. Forster, and K. Rajewsky. 1990. Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation. EMBO J. 9:2133–2140.
   PubMed Web of Science ®Google Scholar
• Gu, H., D. Kitamura, and K. Rajewsky. 1991. B cell development regulated by gene rearrangement: arrest of maturation by membrane-bound D mu protein and selection of DH element reading frames. Cell 65:47–54.
   PubMed Web of Science ®Google Scholar
• Gu, J., H. Lu, B. Tippin, N. Shimazaki, M. F. Goodman, and M. R. Lieber. 2007. XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps. EMBO J. 26:1010–1023.
   PubMedGoogle Scholar
• Heyer, B. S., A. MacAuley, O. Behrendtsen, and Z. Werb. 2000. Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development. Genes Dev. 14:2072–2084.
   PubMed Web of Science ®Google Scholar
• Holmberg, D., A. A. Freitas, D. Portnoi, F. Jacquemart, S. Avrameas, and A. Coutinho. 1986. Antibody repertoires of normal BALB/c mice: B lymphocyte populations defined by state of activation. Immunol. Rev. 93:147–169.
   PubMedGoogle Scholar
• Ichihara, Y., H. Hayashida, S. Miyazawa, and Y. Kurosawa. 1989. Only DFL16, DSP2, and DQ52 gene families exist in mouse immunoglobulin heavy chain diversity gene loci, of which DFL16 and DSP2 originate from the same primordial DH gene. Eur. J. Immunol. 19:1849–1854.
   PubMedGoogle Scholar
• Johnson, M. E., Z. Cheng, V. A. Morrison, S. Scherer, M. Ventura, R. A. Gibbs, E. D. Green, and E. E. Eichler. 2006. Recurrent duplication-driven transposition of DNA during hominoid evolution. Proc. Natl. Acad. Sci. USA 103:17626–17631.
   PubMedGoogle Scholar
• Juarez, R., J. F. Ruiz, S. A. Nick McElhinny, D. Ramsden, and L. Blanco. 2006. A specific loop in human DNA polymerase mu allows switching between creative and DNA-instructed synthesis. Nucleic Acids Res. 34:4572–4582.
   PubMedGoogle Scholar
• Kearney, J. F., and M. Vakil. 1986. Idiotype-directed interactions during ontogeny play a major role in the establishment of the adult B cell repertoire. Immunol. Rev. 94:39–50.
   PubMed Web of Science ®Google Scholar
• Kepler, T. B., M. Borrero, B. Rugerio, S. K. McCray, and S. H. Clarke. 1996. Interdependence of N nucleotide addition and recombination site choice in V(D)J. rearrangement. J. Immunol. 157:4451–4457.
   PubMedGoogle Scholar
• Komori, T., A. Okada, V. Stewart, and F. W. Alt. 1993. Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes. Science 261:1171–1175.
   PubMed Web of Science ®Google Scholar
• Lewis, S. M. 1994. The mechanism of V(D)J joining: lessons from molecular, immunological, and comparative analyses. Adv. Immunol. 56:27–150.
   PubMed Web of Science ®Google Scholar
• Li, Y. S., K. Hayakawa, and R. R. Hardy. 1993. The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. J. Exp. Med. 178:951–960.
   PubMed Web of Science ®Google Scholar
• Lieber, M. R., H. Lu, J. Gu, and K. Schwarz. 2008. Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining: relevance to cancer, aging, and the immune system. Cell Res. 18:125–133.
   PubMed Web of Science ®Google Scholar
• Livak, K. J., and T. D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25:402–408.
   PubMed Web of Science ®Google Scholar
• Lu, C. P., J. E. Posey, and D. B. Roth. 2008. Understanding how the V(D)J. recombinase catalyzes transesterification: distinctions between DNA cleavage and transposition. Nucleic Acids Res. 36:2864–2873.
   PubMedGoogle Scholar
• Lucas, D., T. Lain de Lera, M. A. Gonzalez, J. F. Ruiz, O. Dominguez, J. C. Casanova, A. C. Martinez, L. Blanco, and A. Bernad. 2005. Polymerase mu is up-regulated during the T cell-dependent immune response and its deficiency alters developmental dynamics of spleen centroblasts. Eur. J. Immunol. 35:1601–1611.
   PubMedGoogle Scholar
• Ma, Y., H. Lu, B. Tippin, M. F. Goodman, N. Shimazaki, O. Koiwai, C. L. Hsieh, K. Schwarz, and M. R. Lieber. 2004. A biochemically defined system for mammalian nonhomologous DNA end joining. Mol. Cell 16:701–713.
   PubMed Web of Science ®Google Scholar
• Mahajan, K. N., S. A. Nick McElhinny, B. S. Mitchell, and D. A. Ramsden. 2002. Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair. Mol. Cell. Biol. 22:5194–5202.
   PubMed Web of Science ®Google Scholar
• Marcos, M. A., S. Morales-Alcelay, I. E. Godin, F. Dieterlen-Lievre, S. G. Copin, and M. L. Gaspar. 1997. Antigenic phenotype and gene expression pattern of lymphohemopoietic progenitors during early mouse ontogeny. J. Immunol. 158:2627–2637.
   PubMedGoogle Scholar
• Marleau, A. M., J. D. Greenwood, Q. Wei, B. Singh, and B. A. Croy. 2003. Chimerism of murine fetal bone marrow by maternal cells occurs in late gestation and persists into adulthood. Lab. Investig. 83:673–681.
   PubMed Web of Science ®Google Scholar
• Marshall, A. J., N. Doyen, L. A. Bentolila, C. J. Paige, and G. E. Wu. 1998. Terminal deoxynucleotidyl transferase expression during neonatal life alters D(H) reading frame usage and Ig-receptor-dependent selection of V regions. J. Immunol. 161:6657–6663.
   PubMedGoogle Scholar
• Martin, F., X. Chen, and J. F. Kearney. 1997. Development of VH81X transgene-bearing B cells in fetus and adult: sites for expansion and deletion in conventional and CD5/B1 cells. Int. Immunol. 9:493–505.
   PubMedGoogle Scholar
• Meek, K. 1990. Analysis of junctional diversity during B lymphocyte development. Science 250:820–823.
   PubMed Web of Science ®Google Scholar
• Moon, A. F., M. Garcia-Diaz, V. K. Batra, W. A. Beard, K. Bebenek, T. A. Kunkel, S. H. Wilson, and L. C. Pedersen. 2007. The X family portrait: structural insights into biological functions of X family polymerases. DNA Repair 6:1709–1725.
   PubMed Web of Science ®Google Scholar
• Nadel, B., S. Tehranchi, and A. J. Feeney. 1995. Coding end processing is similar throughout ontogeny. J. Immunol. 154:6430–6436.
   PubMedGoogle Scholar
• Nick McElhinny, S. A., J. M. Havener, M. Garcia-Diaz, R. Juarez, K. Bebenek, B. L. Kee, L. Blanco, T. A. Kunkel, and D. A. Ramsden. 2005. A gradient of template dependence defines distinct biological roles for family X polymerases in nonhomologous end joining. Mol. Cell 19:357–366.
   PubMed Web of Science ®Google Scholar
• Pandey, A., L. W. Tjoelker, and C. B. Thompson. 1993. Restricted immunoglobulin junctional diversity in neonatal B cells results from developmental selection rather than homology-based V(D)J joining. J. Exp. Med. 177:329–337.
   PubMedGoogle Scholar
• Picher, A. J., and L. Blanco. 2007. Human DNA polymerase lambda is a proficient extender of primer ends paired to 7,8-dihydro-8-oxoguanine. DNA Repair 6:1749–1756.
   PubMedGoogle Scholar
• Picher, A. J., M. Garcia-Diaz, K. Bebenek, L. C. Pedersen, T. A. Kunkel, and L. Blanco. 2006. Promiscuous mismatch extension by human DNA polymerase lambda. Nucleic Acids Res. 34:3259–3266.
   PubMedGoogle Scholar
• Rajewsky, K. 1996. Clonal selection and learning in the antibody system. Nature 381:751–758.
   PubMed Web of Science ®Google Scholar
• Ramsden, D. A., C. J. Paige, and G. E. Wu. 1994. Kappa light chain rearrangement in mouse fetal liver. J. Immunol. 153:1150–1160.
   PubMedGoogle Scholar
• Reddy, Y. V., E. J. Perkins, and D. A. Ramsden. 2006. Genomic instability due to V(D)J recombination-associated transposition. Genes Dev. 20:1575–1582.
   PubMedGoogle Scholar
• Rooney, S., J. Chaudhuri, and F. W. Alt. 2004. The role of the non-homologous end-joining pathway in lymphocyte development. Immunol. Rev. 200:115–131.
   PubMed Web of Science ®Google Scholar
• Ruetsch, N. R., G. C. Bosma, and M. J. Bosma. 2000. Unexpected rearrangement and expression of the immunoglobulin λ1 locus in scid mice. J. Exp. Med. 191:1933–1943.
   PubMedGoogle Scholar
• Ruiz, J. F., D. Lucas, E. Garcia-Palomero, A. I. Saez, M. A. Gonzalez, M. A. Piris, A. Bernad, and L. Blanco. 2004. Overexpression of human DNA polymerase mu (Pol mu) in a Burkitt's lymphoma cell line affects the somatic hypermutation rate. Nucleic Acids Res. 32:5861–5873.
   PubMedGoogle Scholar
• Schroeder, H. W., Jr. 2006. Similarity and divergence in the development and expression of the mouse and human antibody repertoires. Dev. Comp. Immunol. 30:119–135.
   PubMed Web of Science ®Google Scholar
• Schroeder, H. W., Jr., J. L. Hillson, and R. M. Perlmutter. 1987. Early restriction of the human antibody repertoire. Science 238:791–793.
   PubMed Web of Science ®Google Scholar
• Strasser, A., A. Rolink, and F. Melchers. 1989. One synchronous wave of B cell development in mouse fetal liver changes at day 16 of gestation from dependence to independence of a stromal cell environment. J. Exp. Med. 170:1973–1986.
   PubMedGoogle Scholar
• Tonegawa, S. 1983. Somatic generation of antibody diversity. Nature 302:575–581.
   PubMed Web of Science ®Google Scholar
• Wasserman, R., Y. S. Li, S. A. Shinton, C. E. Carmack, T. Manser, D. L. Wiest, K. Hayakawa, and R. R. Hardy. 1998. A novel mechanism for B cell repertoire maturation based on response by B cell precursors to pre-B receptor assembly. J. Exp. Med. 187:259–264.
   PubMedGoogle Scholar
• Yokota, T., J. Huang, M. Tavian, Y. Nagai, J. Hirose, J. C. Zuniga-Pflucker, B. Peault, and P. W. Kincade. 2006. Tracing the first waves of lymphopoiesis in mice. Development 133:2041–2051.
   PubMedGoogle Scholar
• Yu, K., and M. R. Lieber. 1999. Mechanistic basis for coding end sequence effects in the initiation of V(D)J. recombination. Mol. Cell. Biol. 19:8094–8102.
   PubMedGoogle Scholar
• Zhang, Y., X. Wu, F. Yuan, Z. Xie, and Z. Wang. 2001. Highly frequent frameshift DNA synthesis by human DNA polymerase mu. Mol. Cell. Biol. 21:7995–8006.
   PubMedGoogle Scholar