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Molecular and Cellular Biology, March 2009, p. 1266-1275, Vol. 29, No. 5
0270-7306/09/$08.00+0     doi:10.1128/MCB.01518-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Role for DNA Polymerase µ in the Emerging DJH Rearrangements of the Postgastrulation Mouse Embryo{triangledown} ,{dagger}

Beatriz Gozalbo-López,1 Paula Andrade,2 Gloria Terrados,2 Belén de Andrés,1 Natalia Serrano,1 Isabel Cortegano,2 Beatriz Palacios,1 Antonio Bernad,3 Luis Blanco,2 Miguel A. R. Marcos,2,{ddagger}* and María Luisa Gaspar1,{ddagger}

Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain,1 Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Campus de Cantoblanco, Madrid 28049, Spain,2 Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, Madrid 28029, Spain3

Received 30 September 2008/ Returned for modification 29 October 2008/ Accepted 12 December 2008

The molecular complexes involved in the nonhomologous end-joining process that resolves recombination-activating gene (RAG)-induced double-strand breaks and results in V(D)J gene rearrangements vary during mammalian ontogeny. In the mouse, the first immunoglobulin gene rearrangements emerge during midgestation periods, but their repertoires have not been analyzed in detail. We decided to study the postgastrulation DJH joints and compare them with those present in later life. The embryo DJH joints differed from those observed in perinatal life by the presence of short stretches of nontemplated (N) nucleotides. Whereas most adult N nucleotides are introduced by terminal deoxynucleotidyl transferase (TdT), the embryo N nucleotides were due to the activity of the homologous DNA polymerase µ (Polµ), which was widely expressed in the early ontogeny, as shown by analysis of Polµ–/– embryos. Based on its DNA-dependent polymerization ability, which TdT lacks, Polµ also filled in small sequence gaps at the coding ends and contributed to the ligation of highly processed ends, frequently found in the embryo, by pairing to internal microhomology sites. These findings show that Polµ participates in the repair of early-embryo, RAG-induced double-strand breaks and subsequently may contribute to preserve the genomic stability and cellular homeostasis of lymphohematopoietic precursors during development.

* Corresponding author. Mailing address: Centro de Biología Molecular, Campus de Cantoblanco, C. Nicolás Cabrera 1, 28049 Madrid, Spain. Phone: 34 911964672. Fax: 34 911964420. E-mail: marmarcos{at}cbm.uam.es

{triangledown} Published ahead of print on 22 December 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} M.A.R.M. and M.L.G. contributed equally as senior leaders of the research.

Molecular and Cellular Biology, March 2009, p. 1266-1275, Vol. 29, No. 5
0270-7306/09/$08.00+0     doi:10.1128/MCB.01518-08
Copyright © 2009, 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]  


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