43. Kevin Ahern's Biochemistry - DNA Repair and Review Session
1. Contact - [email protected] 2. Kevin's lectures with The Great Courses - https://www.thegreatcoursesplus.com/b... 3. Kevin's Lecturio videos for medical students - https://www.lecturio.com/medical-cour... 4. Course materials at https://kevingahern.com/biochemistry-... 5. Course video channel at • 27. Kevin Ahern's Biochemistry - Citric A... 6. Metabolic Melodies at https://teeheetime.com/category/lyric... 7. Kevin's Free Biochemistry books - https://kevingahern.com/biochemistry-... 8. Kevin's Pre-med Audio course on Listenable - https://listenable.io/web/courses/143... DNA Replication/Repair/Recombination III 1. Damage to DNA can occur chemically (deamination of adenine to form hypoxanthine), by oxidation (creation of 8-oxo-guanine by reactive oxygen species reaction), by reaction with an aflatoxin metabolite, by reaction with a cross-linking reagent, such as psoralen, and by dimerization of adjacent thymines stimulated by ultraviolet light. These systems require repair - deescribed below. Another system requiring repair is DNA sliding, which can occur amid repeating sequences. Lack of a repair system for these leads to Huntington's disease. 2. DNA Repair systems to repair damage include A. Proofreading was discussed earlier. It involves 3'-5' exonucleolytic activity of a DNA polymerase and it ccurs as DNA is being replicated. B. Mismatch repair - fixing of mismatches that occur, largely as a result of errors in replication. C. Nucleotide Excision Repair - Excision of a group of nucleotides followed by replacement with correct ones by DNA polymerase. Removal of thymine dimers, for example D. Base excision repair - Excision of a damaged base - for example uracil glycosylase removal of U from DNA 3. In E. coli, mismatch repair occurs as a result of action of the proteins MutS (recognizes mismatch), MutL (recruits MutH), and MutH (nicks newly synthesized strand of DNA to allow exonucleolytic removal of nucleotides around the mismatch). 4. Nucleotide excision repair can be used to repair thymine dimers. Here, a segment of DNA containing the damage is removed by a nuclease. The gap is then filled in using DNA Polymerase and DNA ligase. 5. Base excision repair (uracil repair) involves removal of uracil from DNA followed by nicking by an endonuclease, followed by repair by DNA polymerase and DNA ligase. 6. A critical protein for monitoring DNA for damage prior to division is p53. It can stop the cell cycle if it senses damage and initiate repair. If repair is unable to be performed, p53 can induce cellular suicide - apoptosis.
