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Ubiquitin recognition by FAAP20 expands the complex interface beyond the canonical UBZ domain.

dc.contributor.author D'Andrea, AD
dc.contributor.author Kim, H
dc.contributor.author Wang, S
dc.contributor.author Wojtaszek, JL
dc.contributor.author Wu, Qinglin
dc.contributor.author Zhou, Pei
dc.coverage.spatial England
dc.date.accessioned 2017-01-10T16:11:34Z
dc.date.issued 2014-12-16
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/25414354
dc.identifier gku1153
dc.identifier.uri http://hdl.handle.net/10161/13468
dc.description.abstract FAAP20 is an integral component of the Fanconi anemia core complex that mediates the repair of DNA interstrand crosslinks. The ubiquitin-binding capacity of the FAAP20 UBZ is required for recruitment of the Fanconi anemia complex to interstrand DNA crosslink sites and for interaction with the translesion synthesis machinery. Although the UBZ-ubiquitin interaction is thought to be exclusively encapsulated within the ββα module of UBZ, we show that the FAAP20-ubiquitin interaction extends beyond such a canonical zinc-finger motif. Instead, ubiquitin binding by FAAP20 is accompanied by transforming a disordered tail C-terminal to the UBZ of FAAP20 into a rigid, extended β-loop that latches onto the complex interface of the FAAP20 UBZ and ubiquitin, with the invariant C-terminal tryptophan emanating toward I44(Ub) for enhanced binding specificity and affinity. Substitution of the C-terminal tryptophan with alanine in FAAP20 not only abolishes FAAP20-ubiquitin binding in vitro, but also causes profound cellular hypersensitivity to DNA interstrand crosslink lesions in vivo, highlighting the indispensable role of the C-terminal tail of FAAP20, beyond the compact zinc finger module, toward ubiquitin recognition and Fanconi anemia complex-mediated DNA interstrand crosslink repair.
dc.language eng
dc.relation.ispartof Nucleic Acids Res
dc.relation.isversionof 10.1093/nar/gku1153
dc.subject DNA Repair
dc.subject Fanconi Anemia Complementation Group Proteins
dc.subject Models, Molecular
dc.subject Protein Binding
dc.subject Protein Interaction Domains and Motifs
dc.subject Tryptophan
dc.subject Ubiquitin
dc.title Ubiquitin recognition by FAAP20 expands the complex interface beyond the canonical UBZ domain.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/25414354
pubs.begin-page 13997
pubs.end-page 14005
pubs.issue 22
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Chemistry
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 42
dc.identifier.eissn 1362-4962


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