UBE2T Is the E2 in the Fanconi Anemia Pathway and Undergoes Negative Autoregulation

Yuichi J. Machida, Yuka Machida, Yuefeng Chen, Allan M. Gurtan, Gary M. Kupfer, Alan D. D'Andrea, Anindya Dutta

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

The Fanconi anemia pathway is required for the efficient repair of damaged DNA. A key step in this pathway is the monoubiquitination of the FANCD2 protein by the ubiquitin ligase (E3) composed of Fanconi anemia core complex proteins. Here, we show that UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway. UBE2T binds to FANCL, the ubiquitin ligase subunit of the Fanconi anemia core complex, and is required for the monoubiquitination of FANCD2 in vivo. DNA damage in UBE2T-depleted cells leads to the formation of abnormal chromosomes that are a hallmark of Fanconi anemia. In addition, we show that UBE2T undergoes automonoubiquitination in vivo. This monoubiquitination is stimulated by the presence of the FANCL protein and inactivates UBE2T. Therefore, UBE2T is the E2 in the Fanconi anemia pathway and has a self-inactivation mechanism that could be important for negative regulation of the Fanconi anemia pathway.

Original languageEnglish (US)
Pages (from-to)589-596
Number of pages8
JournalMolecular Cell
Volume23
Issue number4
DOIs
StatePublished - Aug 18 2006

Keywords

  • HUMDISEASE
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'UBE2T Is the E2 in the Fanconi Anemia Pathway and Undergoes Negative Autoregulation'. Together they form a unique fingerprint.

Cite this