The nuclear accumulation of the Fanconi anemia protein FANCE depends on FANCC

DNA Repair
France LéveilléJohan P De Winter

Abstract

The Fanconi anemia (FA) protein FANCE is an essential component of the nuclear FA core complex, which is required for monoubiquitination of the downstream target FANCD2, an important step in the FA pathway of DNA cross-link repair. FANCE is predominantly localized in the nucleus and acts as a molecular bridge between the FA core complex and FANCD2, through direct binding of both FANCC and FANCD2. At present, it is poorly understood how the nuclear accumulation of FANCE is regulated and therefore we investigated the nuclear localization of this FA protein. We found that FANCE has a strong tendency to localize in the nucleus, since the addition of a nuclear export signal does not interfere with the nuclear localization of FANCE. We also demonstrate that the nuclear accumulation of FANCE does not rely solely on its nuclear localization signal motifs, but also on FANCC. The other FA proteins are not involved in the nuclear accumulation of FANCE, indicating a tight relationship between FANCC and FANCE, as suggested from their direct interaction. Finally, we show that the region of FANCE interacting with FANCC appears to be different from the region involved in binding FANCD2. This strengthens the idea that FANCE recruits FANCD2 to t...Continue Reading

References

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Citations

Feb 20, 2007·Nucleic Acids Research·Ravi K NookalaLuca Pellegrini
Jun 8, 2012·Anemia·Charlotte Hodson, Helen Walden
Jun 28, 2012·Anemia·Tagrid Kaddar, Madeleine Carreau
Sep 5, 2009·Critical Reviews in Biochemistry and Molecular Biology·Kerstin Gari, Angelos Constantinou
Dec 9, 2008·Mutation Research·Johan P de Winter, Hans Joenje
Aug 19, 2015·Journal of Molecular Biology·Frédérick BouffardFrancine Durocher

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