Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia.

Cell Rep
Authors
Keywords
Abstract

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.

Year of Publication
2015
Journal
Cell Rep
Volume
12
Issue
1
Pages
35-41
Date Published
2015 Jul 07
ISSN
2211-1247
URL
DOI
10.1016/j.celrep.2015.06.014
PubMed ID
26119737
PubMed Central ID
PMC4497947
Links
Grant list
UL1 TR000043 / TR / NCATS NIH HHS / United States
R01 HL120922 / HL / NHLBI NIH HHS / United States
T32GM007739 / GM / NIGMS NIH HHS / United States
Intramural NIH HHS / United States
8 UL1 TR000043 / TR / NCATS NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States