Lecture 3a - Methylpurine DNA glycosylase (MPG): repair of...

Info iconThis preview shows pages 1–12. Sign up to view the full content.

View Full Document Right Arrow Icon
M ethylp urine DNA g lycosylase (MPG): repair of alkylated bases 7-meG quantitatively the major adduct following Sn1 and Sn2 methylating agents but 3-meA is thought to be the major cytotoxic adduct MPG is only glycosylase that recognizes alkylating lesions in mammals -MPG does not seem to release products generated by chloroethylating agents
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
AP endonucleases and downstream BER proteins • after AP site generated, BER pathway usually proceeds using common set of proteins: • AP endonuclease makes a nick 5’ to the AP site, leaving 3’ hydroxyl and 5’ phosphate termini • the presence of these 5’ and 3’ groups permits a DNA polymerase to fill the gap • a DNA ligase seals the nick • In addition to AP endonuclease activity , these enzymes possess phosphodiesterase activity for removal of fragmented sugar residues, such as phosphoglycolate from 3’ terminus of strand breaks induced by oxidants • this activity can remove 3’ terminal groups left by AP lyases following at AP sites
Background image of page 2
Damage initially processed by glycosylases with 3’ AP lyase activity generally is repaired by the short patch BER pathway Damage initially processed by simple glycosylases use 5’ APE and long patch BER
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
hOGG1 catalytic site
Background image of page 4
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 6
Lecture 3 Overview •Photo lyas es • Nucleotide Excision Repair –overview -historical -what does it fix -how does it fix
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Photolyases-what we don’t have • direct mode of repair • bind to DNA damage induced by UV light in a light-independent fashion • the repair process is driven by exposure to light • revert both cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts • -NOT in placental mammals but in marsupials and everything else
Background image of page 8
Photolyases
Background image of page 9

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Nucleotide Excision Repair- Overview • bulky adducts • helix distortion sensing mechanism • originally due to UV light • three diseases
Background image of page 10
NER-what does it fix? • repairs adducts of chemicals covalently bond to DNA • the structure of the agent and the means through which it binds to DNA are diverse • e.g. acetylaminofluorene-guanine cisplatin-guanine psoralen-thymine thymine dimers 6-4 photoproducts • common feature:lesions that cause major helical distortion, and the chemical-DNA adduct is ‘bulky’
Background image of page 11

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 12
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 12/03/2010 for the course PHAMACOLOG pcl470 taught by Professor Arnot during the Fall '10 term at University of Toronto- Toronto.

Page1 / 27

Lecture 3a - Methylpurine DNA glycosylase (MPG): repair of...

This preview shows document pages 1 - 12. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online