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

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

Category:

Science & Technology

Tags:

• ROS
• RNS
• XRCC1
• APE1
• DNA polymerase B
• Base
• excision
• repair
• reactive
• oxygen
• spices
• nitrogen
• short
• patch
• dna
• mitochondria
• ageing
• aging
• neurodegeneration
• carcinogenesis
• mutagenesis
• cancer
• SSB

[pmendez01]

Thanks for your comments.

[MolMed2010]

What is mediating helicase activity??? :(?



[AudunHB]

4. The view of BER as a succession of recruitments of BER factors is probably an artefact of a reductionistic theoretical approach (In vitro experiments by biochemists). XRCC1 is a scaffold protein that assembles large complexes of BER factors. XRCC1 stability is in large parts determined by strong binding to LigIII and also Polymerase Beta. It further interacts/binds glycosylases, APE1, PARP1, PARP2, PNK, APTX, APLF, PCNA and itself (dimers/multimers).

[AudunHB]

3. Only the N-terminal domain of XRCC1 has been crystalized, but there's no indication that XRCC1 is a DNA clamp like PCNA (circular around DNA) and it certainly has not been observed to scan DNA (as the animation suggests).

[AudunHB]

2. The DNA backbone of AP sites is cleaved by either bifunctional glycosylases or APE1 (AP endonuclease 1)

[illusyo90]

amazing video... thanks for this and for the explanation!!



[retlifwolley]

Great