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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter CONJUGATING ENZYME UBC13; SOMATIC HYPERMUTATION; DNA-DAMAGE; UBIQUITIN; REPAIR; INTERMEDIATE; RECOGNITION; MECHANISMS; PROTEINS; BREAKS
Sprache englisch
Veröffentlichungsjahr 2010
HGF-Berichtsjahr 2010
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Zeitschrift Nucleic Acids Research
Quellenangaben Band: 38, Heft: 14, Seiten: 4701-4707 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501400-001
PubMed ID 20223767
DOI 10.1093/nar/gkq154
WOS ID 000280922400021
Scopus ID 77955808766
Erfassungsdatum 2010-10-31
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