Fanconi anemia (FA) is a rare bone marrow failure and cancer predisposition syndrome resulting from pathogenic mutations in genes encoding proteins participating in the repair of DNA interstrand crosslinks (ICLs). Mutations in 17 genes (FANCA-FANCS) have been identified in FA patients, defining 17 complementation groups. Here, we describe an individual presenting with typical FA features who is deficient for the ubiquitin-conjugating enzyme (E2), UBE2T. UBE2T is known to interact with FANCL, the E3 ubiquitin-ligase component of the multiprotein FA core complex, and is necessary for the monoubiquitination of FANCD2 and FANCI. Proband fibroblasts do not display FANCD2 and FANCI monoubiquitination, do not form FANCD2 foci following treatment with mitomycin C, and are hypersensitive to crosslinking agents. These cellular defects are complemented by expression of wild-type UBE2T, demonstrating that deficiency of the protein UBE2T can lead to Fanconi anemia. UBE2T gene gains an alias of FANCT.
Cell Rep. 2015 Jul 7;12(1):35-41. doi: 10.1016/j.celrep.2015.06.014. Epub 2015 Jun 25.
Rickman KA1, Lach FP1, Abhyankar A2, Donovan FX3, Sanborn EM1, Kennedy JA1, Sougnez C4, Gabriel SB4, Elemento O5, Chandrasekharappa SC3, Schindler D6, Auerbach AD7, Smogorzewska A8.
1 Laboratory of Genome Maintenance, The Rockefeller University, New York, NY 10065, USA.
2 New York Genome Center, New York, NY 10013, USA.
3 Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
4 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
5 Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10021, USA.
6 Institute for Human Genetics, Biozentrum, Universität Würzburg, 97074 Würzburg, Germany.
7 Human Genetics and Hematology, The Rockefeller University, New York, NY 10065, USA.
8 Laboratory of Genome Maintenance, The Rockefeller University, New York, NY 10065, USA.
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