A role for DNA polymerase ¿ in the emerging DJH rearrangements of the postgastrulation mouse embryo

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Gozalbo López, B (Author) Other; Paula B Andrade (Author) FFUP; Terrados, G (Author) Other; De Andrés, B (Author) Other; Serrano, N (Author) Other; Cortegano, I (Author) Other; Palacios, B (Author) Other; Bernad, A (Author) Other; Blanco, L (Author) Other; Marcos, MAR (Author) Other; Gaspar, ML (Author) Other

Journal

Title: Molecular and Cellular Biology

Vol. 29

Pages: 1266-1275

ISSN: 0270-7306

Publisher: American Society for Microbiology

Indexing

Scopus - 23 Citations

Other information

Authenticus ID: P-00N-FBV

DOI: 10.1128/mcb.01518-08

Abstract (EN): 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 ¿ (Pol¿), which was widely expressed in the early ontogeny, as shown by analysis of Pol¿-/- embryos. Based on its DNA-dependent polymerization ability, which TdT lacks, Pol¿ 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 Pol¿ 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. Copyright

Language: English

Type (Professor's evaluation): Scientific