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Article: Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair

TitleFanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair
Authors
Issue Date2012
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2012, v. 109 n. 12, p. 4491-4496 How to Cite?
Abstract
The Fanconi anemia (FA) pathway participates in interstrand crosslink (ICL) repair and the maintenance of genomic stability. The FA core complex consists of eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and FAAP100). The FA core complex has ubiquitin ligase activity responsible for monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a cascade of biochemical events that allow processing and removal of crosslinked DNA and thereby promotes cell survival following DNA damage. Here, we report the identification of a unique component of the FA core complex, namely, FAAP20, which contains a RAD18- like ubiquitin-binding zinc-finger domain. Our data suggest that FAAP20 promotes the functional integrity of the FA core complex via its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout cells devoid of FAAP20 displayed the hallmarks of FA cells, including hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced FANCD2 monoubiquitination. Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway.
Persistent Identifierhttp://hdl.handle.net/10722/149784
ISSN
2013 Impact Factor: 9.809
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Cancer Prevention Research Institute of TexasRP110465-P2
Department of DefenseW81XWH-05-1-0470
MD Anderson Cancer CenterCA016672
Funding Information:

We thank our colleagues in the J.C. laboratory for insightful discussions and technical assistance. This work was supported in part by the Cancer Prevention Research Institute of Texas, Multi-Investigator Award, Grant RP110465-P2 (to J.C.). J.C. is a recipient of Era of Hope Scholar Award W81XWH-05-1-0470 from the Department of Defense and a member of the MD Anderson Cancer Center (CA016672).

References

 

Author Affiliations
  1. The University of Hong Kong
  2. University of Texas M. D. Anderson Cancer Center
DC FieldValueLanguage
dc.contributor.authorLeung, JWCen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorFong, KWen_US
dc.contributor.authorHuen, MSYen_US
dc.contributor.authorLi, Len_US
dc.contributor.authorChen, Jen_US
dc.date.accessioned2012-06-26T05:58:33Z-
dc.date.available2012-06-26T05:58:33Z-
dc.date.issued2012en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2012, v. 109 n. 12, p. 4491-4496en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/149784-
dc.description.abstractThe Fanconi anemia (FA) pathway participates in interstrand crosslink (ICL) repair and the maintenance of genomic stability. The FA core complex consists of eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and FAAP100). The FA core complex has ubiquitin ligase activity responsible for monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a cascade of biochemical events that allow processing and removal of crosslinked DNA and thereby promotes cell survival following DNA damage. Here, we report the identification of a unique component of the FA core complex, namely, FAAP20, which contains a RAD18- like ubiquitin-binding zinc-finger domain. Our data suggest that FAAP20 promotes the functional integrity of the FA core complex via its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout cells devoid of FAAP20 displayed the hallmarks of FA cells, including hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced FANCD2 monoubiquitination. Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshChromosome Aberrationsen_US
dc.subject.meshCross-Linking Reagents - Chemistryen_US
dc.subject.meshDna Repairen_US
dc.subject.meshFanconi Anemia - Metabolismen_US
dc.subject.meshFanconi Anemia Complementation Group A Protein - Metabolismen_US
dc.subject.meshFanconi Anemia Complementation Group Proteins - Metabolismen_US
dc.subject.meshGene Deletionen_US
dc.subject.meshHek293 Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshMitomycin - Chemistryen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshProtein Structure, Tertiaryen_US
dc.subject.meshSequence Homology, Amino Aciden_US
dc.subject.meshUbiquitin - Chemistryen_US
dc.subject.meshZinc Fingersen_US
dc.titleFanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repairen_US
dc.typeArticleen_US
dc.identifier.emailHuen, MSY:huen.michael@hku.hken_US
dc.identifier.authorityHuen, MSY=rp01336en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1073/pnas.1118720109en_US
dc.identifier.pmid22396592en_US
dc.identifier.pmcidPMC3311328-
dc.identifier.scopuseid_2-s2.0-84863350996-
dc.identifier.hkuros198701-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84858697395&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume109en_US
dc.identifier.issue12en_US
dc.identifier.spage4491en_US
dc.identifier.epage4496en_US
dc.identifier.isiWOS:000301712600034-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLeung, JWC=55114129700en_US
dc.identifier.scopusauthoridWang, Y=55114782900en_US
dc.identifier.scopusauthoridFong, KW=55117618900en_US
dc.identifier.scopusauthoridHuen, MSY=23004751500en_US
dc.identifier.scopusauthoridLi, L=55115480500en_US
dc.identifier.scopusauthoridChen, J=55114141100en_US
dc.identifier.citeulike10652501-

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