title: Direct DNA binding activity of the Fanconi anemia D2 protein.
abstract: It is known that the Fanconi anemia D2 protein is vital for protecting the genome from DNA damage, but what activities this protein has are unknown. In these experiments we purified full-length Fanconi anemia protein D2 (FANCD2), and we found that FANCD2 bound to DNA with specificity for certain structures: double strand DNA ends and Holliday junctions. Proteins containing patient-derived mutations or artificial variants of the FANCD2 protein were similarly expressed and purified, and each variant bound to the Holliday junction DNA with similar affinity as did the wild-type protein. There was no single discrete domain of FANCD2 protein that bound to DNA, but rather the full-length protein was required for structure-specific DNA binding. This finding of DNA binding is the first biochemical activity identified for this key protein in the Fanconi anemia pathway.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Woo-Hyun
authors.initials: WH
authors.lastname: Park
authors.forename: Steven
authors.initials: S
authors.lastname: Margossian
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Horwitz
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Simons
authors.forename: Alan D
authors.initials: AD
authors.lastname: D'Andrea
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Parvin
mesh_terms: D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D052236:Fanconi Anemia Complementation Group D2 Protein; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D004247:DNA