5a39

Structure of Rad14 in complex with cisplatin containing DNA

spinqualitylabelsall models 5a39, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5a39 is a 8 chain structure with sequence from Atcc 18824 and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CPT, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [RAD14_YEAST] Involved in nucleotide excision repair. Binds specifically to damaged DNA. Required for the incision step. Publication Abstract from PubMed Nucleotide excision repair (NER) is responsible for the removal of a large variety of structurally diverse DNA lesions. Mutations of the involved proteins cause the xeroderma pigmentosum (XP) cancer predisposition syndrome. Although the general mechanism of the NER process is well studied, the function of the XPA protein, which is of central importance for successful NER, has remained enigmatic. It is known, that XPA binds kinked DNA structures and that it interacts also with DNA duplexes containing certain lesions, but the mechanism of interactions is unknown. Here we present two crystal structures of the DNA binding domain (DBD) of the yeast XPA homolog Rad14 bound to DNA with either a cisplatin lesion (1,2-GG) or an acetylaminofluorene adduct (AAF-dG). In the structures, we see that two Rad14 molecules bind to the duplex, which induces DNA melting of the duplex remote from the lesion. Each monomer interrogates the duplex with a beta-hairpin, which creates a 13mer duplex recognition motif additionally characterized by a sharp 70 degrees DNA kink at the position of the lesion. Although the 1,2-GG lesion stabilizes the kink due to the covalent fixation of the crosslinked dG bases at a 90 degrees angle, the AAF-dG fully intercalates into the duplex to stabilize the kinked structure. Structural insights into the recognition of cisplatin and AAF-dG lesion by Rad14 (XPA).,Koch SC, Kuper J, Gasteiger KL, Simon N, Strasser R, Eisen D, Geiger S, Schneider S, Kisker C, Carell T Proc Natl Acad Sci U S A. 2015 Jun 22. pii: 201508509. PMID:26100901 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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