Modularized Functions of the Fanconi Anemia Core Complex

Yaling Huang, Justin W.C. Leung, Megan Lowery, Nobuko Matsushita, Yucai Wang, Xi Shen, Do Huong, Minoru Takata, Junjie Chen, Lei Li

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

The Fanconi anemia (FA) core complex provides the essential E3 ligase function for spatially defined FANCD2 ubiquitination and FA pathway activation. Of the seven FA gene products forming the core complex, FANCL possesses a RING domain with demonstrated E3 ligase activity. The other six components do not have clearly defined roles. Through epistasis analyses, we identify three functional modules in the FA core complex: a catalytic module consisting of FANCL, FANCB, and FAAP100 is absolutely required for the E3 ligase function, and the FANCA-FANCG-FAAP20 and the FANCC-FANCE-FANCF modules provide nonredundant and ancillary functions that help the catalytic module bind chromatin or sites of DNA damage. Disruption of the catalytic module causes complete loss of the core complex function, whereas loss of any ancillary module component does not. Our work reveals the roles of several FA gene products with previously undefined functions and a modularized assembly of the FA core complex.

Original languageEnglish (US)
Pages (from-to)1849-1857
Number of pages9
JournalCell Reports
Volume7
Issue number6
DOIs
StatePublished - Jun 26 2014
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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