title: DNA bending by the human damage recognition complex XPC-HR23B.
abstract: Genome integrity is maintained, despite constant assault on DNA, due to the action of a variety of DNA repair pathways. Nucleotide excision repair (NER) protects the genome from the deleterious effects of UV irradiation as well as other agents that induce chemical changes in DNA bases. The mechanistic steps required for eukaryotic NER involve the concerted action of at least six proteins or protein complexes. The specificity to incise only the DNA strand including the damage at defined positions is determined by the coordinated assembly of active protein complexes onto damaged DNA. In order to understand the molecular mechanism of the NER reactions and the origin of this specificity and control we analyzed the architecture of functional NER complexes at nanometer resolution by scanning force microscopy (SFM). In the initial step of damage recognition by XPC-HR23B we observe a protein induced change in DNA conformation. XPC-HR23B induces a bend in DNA upon binding and this is stabilized at the site of damage. We discuss the importance of the XPC-HR23B-induced distortion as an architectural feature that can be exploited for subsequent assembly of an active NER complex.
authors.affiliation: Department of Cell Biology and Genetics, Erasmus MC, PO Box 1738, 3000 DR, Rotterdam, The Netherlands.
authors.forename: Ana
authors.initials: A
authors.lastname: Janićijević
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
authors.forename: Nils
authors.initials: N
authors.lastname: Wijgers
authors.forename: Miodrag
authors.initials: M
authors.lastname: Djurica
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.forename: Claire
authors.initials: C
authors.lastname: Wyman
mesh_terms: D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D018625:Microscopy, Atomic Force
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C086984:XPC protein, human; D004247:DNA