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The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL.

Miles, Jennifer A., Frost, Mark G., Carroll, Eilis, Rowe, Michelle L., Howard, Mark J., Sidhu, Ateesh, Chaugule, Viduth K., Alpi, Arno F., Walden, Helen (2015) The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL. Journal of Biological Chemistry, 290 (34). pp. 20995-21006. ISSN 0021-9258. (doi:10.1074/jbc.M115.675835) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:50305)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://doi.org/10.1074/jbc.M115.675835

Abstract

The Fanconi Anemia (FA) DNA repair pathway is essential for the recognition and repair of DNA interstrand crosslinks (ICL). Inefficient repair of these ICL can lead to leukemia and bone marrow failure. A critical step in the pathway is the monoubiquitination of FANCD2 by the RING E3 ligase FANCL. FANCL comprises 3 domains, a RING domain that interacts with E2 conjugating enzymes, a central domain required for substrate interaction, and an N-terminal E2-like fold (ELF) domain. The ELF domain is found in all FANCL homologues, yet the function of the domain remains unknown. We report here that the ELF domain of FANCL is required to mediate a non-covalent interaction between FANCL and ubiquitin. The interaction involves the canonical Ile44 patch on ubiquitin, and a functionally conserved patch on FANCL. We show that the interaction is not necessary for the recognition of the core complex, it does not enhance the interaction between FANCL and Ube2T, and is not required for FANCD2 monoubiquitination in vitro. However, we demonstrate that the ELF domain is required to promote efficient DNA damage-induced FANCD2 monoubiquitination in vertebrate cells, suggesting an important function of ubiquitin binding by FANCL in vivo.

Item Type: Article
DOI/Identification number: 10.1074/jbc.M115.675835
Uncontrolled keywords: DNA repair E3 ubiquitin ligase isothermal titration calorimetry (ITC) nuclear magnetic resonance (NMR) ubiquitin structure
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Susan Davies
Date Deposited: 26 Aug 2015 15:17 UTC
Last Modified: 29 May 2019 15:57 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/50305 (The current URI for this page, for reference purposes)
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