2vbj

Molecular basis of human XPC gene recognition and cleavage by engineered homing endonuclease heterodimers

spinqualitylabelsall models 2vbj, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vbj is a 4 chain structure with sequence from Chlre. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Related: 1g9z, 1bp7, 2vbl, 1af5, 2vbo, 1mow, 1g9y, 2vbn, 1n3f, 1t9i, 1u0d, 1t9j, 1n3e, 1u0c Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DNE1_CHLRE] Endonuclease involved in group I intron homing. Recognizes and cleaves a 19-24 bp palindromic DNA site. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Xeroderma pigmentosum is a monogenic disease characterized by hypersensitivity to ultraviolet light. The cells of xeroderma pigmentosum patients are defective in nucleotide excision repair, limiting their capacity to eliminate ultraviolet-induced DNA damage, and resulting in a strong predisposition to develop skin cancers. The use of rare cutting DNA endonucleases-such as homing endonucleases, also known as meganucleases-constitutes one possible strategy for repairing DNA lesions. Homing endonucleases have emerged as highly specific molecular scalpels that recognize and cleave DNA sites, promoting efficient homologous gene targeting through double-strand-break-induced homologous recombination. Here we describe two engineered heterodimeric derivatives of the homing endonuclease I-CreI, produced by a semi-rational approach. These two molecules-Amel3-Amel4 and Ini3-Ini4-cleave DNA from the human XPC gene (xeroderma pigmentosum group C), in vitro and in vivo. Crystal structures of the I-CreI variants complexed with intact and cleaved XPC target DNA suggest that the mechanism of DNA recognition and cleavage by the engineered homing endonucleases is similar to that of the wild-type I-CreI. Furthermore, these derivatives induced high levels of specific gene targeting in mammalian cells while displaying no obvious genotoxicity. Thus, homing endonucleases can be designed to recognize and cleave the DNA sequences of specific genes, opening up new possibilities for genome engineering and gene therapy in xeroderma pigmentosum patients whose illness can be treated ex vivo. Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases.,Redondo P, Prieto J, Munoz IG, Alibes A, Stricher F, Serrano L, Cabaniols JP, Daboussi F, Arnould S, Perez C, Duchateau P, Paques F, Blanco FJ, Montoya G Nature. 2008 Nov 6;456(7218):107-11. PMID:18987743 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Endonuclease

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