title: Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway.
abstract: Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the ~300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each protein has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Woo
authors.initials: W
authors.lastname: Joo
authors.forename: Guozhou
authors.initials: G
authors.lastname: Xu
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Persky
authors.forename: Agata
authors.initials: A
authors.lastname: Smogorzewska
authors.forename: Derek G
authors.initials: DG
authors.lastname: Rudge
authors.forename: Olga
authors.initials: O
authors.lastname: Buzovetsky
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
authors.forename: Nikola P
authors.initials: NP
authors.lastname: Pavletich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000737:chemistry* / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D025801:Ubiquitin / Q000737:chemistry; D054875:Ubiquitination
chemical_list: D004277:DNA, Single-Stranded; C559748:FANCI protein, mouse; C499904:Fancd2 protein, mouse; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins; D025801:Ubiquitin; D004247:DNA