PuSH - Publication Server of Helmholtz Zentrum München: Ubc13 dosage is critical for immunoglobulin gene conversion and gene targeting in vertebrate cells.

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Ertongur, I. ; Tomi, N.S. ; Kutzera, A. ; Fischer-Burkart, S. ; Jungnickel, B.

Ubc13 dosage is critical for immunoglobulin gene conversion and gene targeting in vertebrate cells.

Nucleic Acids Res. 38, 4701-4707 (2010)

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In contrast to lower eukaryotes, most vertebrate cells are characterized by a moderate efficiency of homologous recombination (HR) and limited feasibility of targeted genetic modifications. As a notable exception, the chicken DT40 B cell line is distinguished by efficient homology-mediated repair of DNA lesions during Ig gene conversion, and also shows exceptionally high gene-targeting efficiencies. The molecular basis of these phenomena is elusive. Here we show that the activity levels of Ubc13, the E2 enzyme responsible for non-canonical K63-linked polyubiquitination, are critical for high efficiency of Ig gene conversion and gene targeting in DT40. Ubc13(+/-) cells show substantially lower homology-mediated repair, yet do not display changes in somatic hypermutation, overall DNA repair or cell proliferation. Our results suggest that modulation of the activity of K63-linked polyubiquitination may be used to customize HR efficiencies in vertebrate cells.

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