Base-Excision Repair- DNA Glycosylases
Overview:
- Involves battery of enzyme called → DNA Glycosylases
- Each of which recognise a specific type of altered base in DNA and catalyses its hydrolytic removal.
- Certain errors are too subtle to cause a distortion large enough to be recognised by the general repair systems.
- Free radicals (O2-) can damage DNA, commion nucleotide modification (8-oxoguanine).
- There are at-least 6 types of these enzymes, including those that remove deminated Cs and As, different types of alkylated or oxidised bases, bases with opened rings and bases in which a C=C double bond has accidentally been converted to C-C single bond. So in summary these enzyme remove:
- Oxidised bases → e.g. ( 8-oxoguanine)
- Alkylated bases → e.g. ( 3-methyladenine, 7-methylguanosine)
- Deaminated bases → e.g. (hypoxanthine formed from deamination of adenine. Xanthine formed from deamination of guanine) and (Uracil inappropriately incorporated in DNA or formed by deamination of cytosine)
- Each DNA glycosylate is generally specific for one type of lesion.
- DNA glycosylase cleaves glycosidic bond leaving deoxyribose residue.
- The cleavage creats an apurinic or apyrimidine site (AP site)
E.g. Uracil DNA Glycosylases (Extra not important for exams)
- Specifically remove uracil from DNA, formed by spontaneous deamination of cytosine.
- Mutant cells that lack this enzyme have high rate of G-T and A-T mutations.
- Important in removal of Uracil from DNA!
Steps of Base-Excision Repair
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