Methods for labeling dna ends with halogenated nucleotides...

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/68 (2006.01) C07H 21/00 (2006.01) C07K 16/44 (2006.01) C12P 19/34 (2006.01)

Patent

CA 2230753

The invention pertains to the field of DNA detection for basic research, medical diagnostic testing, and forensic testing. Methods are provided for the end labeling of DNA strands. The DNA strands are first incubated with a halogenated deoxynucleotide triphosphate, such as brominated deoxyuridine triphosphate (BrdUTP), and an enzyme which can catalyze the addition of the halogenated deoxynucleotide to the 3'OH ends of the DNA strand, such as terminal deoxynucleotide transferase (TdT). The resulting modified DNA strands are then incubated with a labeled antibody, such as a fluoresceinated monoclonal antibody, that specifically binds to the halogenated deoxynucleotide. The label is then detected, e.g., by flow cytometry. The methods have utility in detecting apoptosis, in detecting DNA synthesis and/or repair, and as general methods for end labeling of DNA.

L'invention concerne, dans le domaine de la détection d'ADN aux fins de la recherche fondamentale, des analyses de diagnostic médical et des analyses de police scientifique, des méthodes de marquage d'extrémité des brins d'ADN. Les brins d'ADN sont d'abord incubés avec un triphosphate de désoxynucléotide halogéné, comme le triphosphate de désoxyuridine bromuré (BrdUTP) et une enzyme capable de catalyser l'addition du désoxynucléotide halogéné sur les extrémités 3'OH du brin d'ADN, par exemple la désoxynucléotidyle transférase terminale (TdT). Les brins d'ADN modifiés résultants sont ensuite incubés avec un anticorps marqué, par exemple un anticorps monoclonal fluorescéiné, qui se lie spécifiquement au désoxynucléotide halogéné. Le marqueur est ensuite détecté, par exemple par cytométrie de flux. Les procédés sont utiles à la détection de l'apoptose, de la synthèse et/ou de la réparation d'ADN, et comme procédés généraux de marquage d'extrémité d'ADN.

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