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

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TitleFanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair
AuthorsLeung, JWC2
Wang, Y2
Fong, KW2
Huen, MSY1
Li, L2
Chen, J
Issue Date2012
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
CitationProceedings Of The National Academy Of Sciences Of The United States Of America, 2012, v. 109 n. 12, p. 4491-4496 [How to Cite?]
DOI: http://dx.doi.org/10.1073/pnas.1118720109
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.
ISSN0027-8424
2011 Impact Factor: 9.681
2011 SCImago Journal Rankings: 1.754
DOIhttp://dx.doi.org/10.1073/pnas.1118720109
ISI Accession Number IDWOS:000301712600034
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).

PubMed Central IDPMC3311328
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLeung, JWC
dc.contributor.authorWang, Y
dc.contributor.authorFong, KW
dc.contributor.authorHuen, MSY
dc.contributor.authorLi, L
dc.contributor.authorChen, J
dc.date.accessioned2012-06-26T05:58:33Z
dc.date.available2012-06-26T05:58:33Z
dc.date.issued2012
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.
dc.description.natureLink_to_OA_fulltext
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2012, v. 109 n. 12, p. 4491-4496 [How to Cite?]
DOI: http://dx.doi.org/10.1073/pnas.1118720109
dc.identifier.citeulike10652501
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.1118720109
dc.identifier.epage4496
dc.identifier.hkuros198701
dc.identifier.isiWOS:000301712600034
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).

dc.identifier.issn0027-8424
2011 Impact Factor: 9.681
2011 SCImago Journal Rankings: 1.754
dc.identifier.issue12
dc.identifier.pmcidPMC3311328
dc.identifier.pmid22396592
dc.identifier.scopuseid_2-s2.0-84863350996
dc.identifier.spage4491
dc.identifier.urihttp://hdl.handle.net/10722/149784
dc.identifier.volume109
dc.languageeng
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
dc.publisher.placeUnited States
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.relation.referencesReferences in Scopus
dc.subject.meshAmino Acid Sequence
dc.subject.meshChromosome Aberrations
dc.subject.meshCross-Linking Reagents - Chemistry
dc.subject.meshDna Repair
dc.subject.meshFanconi Anemia - Metabolism
dc.subject.meshFanconi Anemia Complementation Group A Protein - Metabolism
dc.subject.meshFanconi Anemia Complementation Group Proteins - Metabolism
dc.subject.meshGene Deletion
dc.subject.meshHek293 Cells
dc.subject.meshHumans
dc.subject.meshMitomycin - Chemistry
dc.subject.meshMolecular Sequence Data
dc.subject.meshMutation
dc.subject.meshProtein Binding
dc.subject.meshProtein Structure, Tertiary
dc.subject.meshSequence Homology, Amino Acid
dc.subject.meshUbiquitin - Chemistry
dc.subject.meshZinc Fingers
dc.titleFanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. University of Texas M. D. Anderson Cancer Center