HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Seki, S. Articles by Ishiai, M. Search for Related Content PubMed Articles by Seki, S. Articles by Ishiai, M.

¹ Department of Immunology and Molecular Genetics, and ² Department of Rehabilitation Medicine, and ³ Department of Nephrology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
⁴ Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Okayama 700-8558, Japan
⁵ Laboratory of Molecular Genetics, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan

The rare hereditary disorder Fanconi anemia (FA) can be caused by mutations in components of the FA core complex (FancA/B/C/E/F/G/L/M), a key regulator FancD2, the breast cancer susceptibility protein BRCA2/FancD1, or the newly identified FancJ/BRIP1 helicase. By performing yeast two-hybrid (Y2H) screens using N-terminal chicken (ch) FancD2 as a bait, we have identified chFancL, the likely ubiquitin E3 ligase subunit of the FA core complex. We also found that ectopically expressed FancD2 and FancL co-immunoprecipitated in 293T cells, and this interaction was dependent on the PHD domain of FancL. FANCL-disrupted chicken DT40 cells displayed defects in both FancD2 monoubiquitination and focus formation. Importantly, cell lines lacking the FANCL or FANCD2 genes, or carrying a "knock-in" mutation of the FancD2 monoubiquitination site (where the Lys 563 residue is changed to Arg), displayed quantitatively identical defects in the repair of I-SceI-induced chromosomal breaks by homologous recombination (HR). These data establish the role of FANCL and FancD2 monoubiquitination in HR repair.

^aThese authors contributed equally to this work.

^bPresent address: Department of Human Genetics, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553 Japan.

*Correspondence: E-mail: minorut{at}hiroshima-u.ac.jp