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DNA repair : Base excision repair SHORT patch v 1.0 - Full HD

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  • Provider: YouTube Link: http://www.youtube.com/watch?v=72oT6N90iWc
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  • Description: DNA repair : Base excision repair short patch - Full HD

    Base excision repair (BER) pathway, protects both nuclear and mitochondrial DNA from "spontaneous DNA damage", mainly generated by eactive oxigen spices (ROS) produced by the normal metabolism of the cell. The spectrum of nucleotide base lesions includes: spontaneous or enzyme-induced deamination, oxidation or alkylation.
    The starrings of the BER pathway are the glycosylases enzymes. They are the DNA-damage sensors and have evolved to selectively detect different kinds of DNA insults. An important trait of the glycosylases consists in their substrate redundance, as demonstrated by mouse models lacking one glycosylase, wich triggers mild consecuences. The glycosylases can be classified as monofunctional, when, only posses the N-glycosylase function, so exclusively removes the damaged nitrogenated base of the nucleotide. When additionally has an AP-lyase activity to remove the deoxyribophosphate (dRP), generating an abasic (AP) site, they are considered as bifunctional glycosylases.

    MONOFUNCTIONAL DNA Glycosylases:
    - MPG
    - UNG-1
    - UNG2
    - SMUG
    - MBD4
    - TDG
    - MYH

    BIFUNCTIONAL DNA Glycosylases:
    - OGG1
    - NTH
    - NEIL-1
    - NEIL-2

    Main steps of BER short pathway
    1- A depurinized, oxydized or alkylated nucleotide base is generated spontaneously or by metabolic-generated reactive oxygen species..
    2- A DNA glysosylase specifically detects the damaged nitrogenated base of the nucleotide and removes it.
    3- The XRCC1 protein, brings APE1 nuclease into the damage site, where will use its AP-lyase activity for cleaving the 5' extrem of the phosphodiester bond. generating an abasic (AP) site.
    4- DNA polymerase β will cleave the 3' extrem of the phosphodiester bond, generating an abasic (AP) site. Then, fills the abasic gap by introducing a complementary nucleotide..
    5- Ligase III, acompanied by the scaffolding protein XRCC1, seals the gap.

    Bibliography:
    Gougang Xu, et al.(2008). Base excision repair, aging and health span. Mech Ageing Dev. 129: 366-382
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