C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/55 (2006.01) A61K 38/46 (2006.01) A61P 17/16 (2006.01) A61P 35/00 (2006.01) C07H 21/02 (2006.01) C07H 21/04 (2006.01) C12N 9/16 (2006.01) C12N 9/22 (2006.01) C12Q 1/44 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2330237
The present disclosure describes DNA damage endonucleases which exhibit broad specificity with respect to the types of structural aberrations in double stranded DNA. These enzymes recognize double stranded DNA with distortions in structure, wherein the distortions result from photoproducts, alkylation, intercalation, abasic sites, mismatched base pairs, cisplatin adducts and inappropriately incorporated bases (for example, 8-oxoguanine, inosine, xanthine, among others). The UVDE (Uvelp) of Schizosaccharomyces pombe, certain truncated forms of that UVDE (lacking from about 100 to about 250 amino acids of N-terminal sequence) and certain endonucleases from Homo sapiens, Neurospora crassa, Bacillus subtilis, and from Deinococcus radiodurans. The present disclosure further provides methods for cleaving double stranded DNA having structural distortions as set forth herein using the exemplified endonucleases or their stable, functional truncated derivatives.
La présente invention concerne des endonucléases de lésion de l'ADN présentant une large spécificité par rapport aux types d'aberrations de structure dans un ADN double brin. Ces enzymes reconnaissent un ADN double brin présentant des distorsions dans sa structure, les distorsions résultant de photoproduits, d'une alkylation, d'une insertion, de sites abasiques, de paires de bases non correspondantes, de composés d'addition de cisplatine et de bases à incorporation inadéquate (par exemple 8-oxoguanine, inosine, xanthine, notamment). L'invention concerne également l'UVDE (Uve1p) de Schizosaccharomyces pombe, certaines formes tronquées de l'UVDE (auxquelles il manque environ entre 100 et 250 acides aminés de la séquence N-terminal) et certaines endonucléases provenant de Homo sapiens, Neurospora crassa, Bacillus subtili et de Deinococcus radiodurans. La présente invention concerne en outre des méthodes de clivage d'un ADN double brin présentant des distorsions de structure telles que celles invoquées ici, les méthodes consistant à utiliser les endonucléases prises comme exemples ou leurs dérivés tronqués stables et fonctionnels.
Avery Angela M.
Doetsch Paul W.
Kaur Balveen
Emory University
Mckay-Carey & Company
LandOfFree
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