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- 1. DNA REPAIR MECHANISMS Created By Junaed Ahmed REG:2011433036 DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY SHAHJALAL UNIVERSITY OF SCIENCE AND TECHNOLOGY
- 2. DNA Repair Mechanisms DOUBLE STRAND BREAKS SINGLE STRAND DAMAGE BASE EXCISION REPAIR MISMATCH REPAIR NUCLEOTIDE EXCISION REPAIR NON- HOMOLOGOUS END JOINING HOMOLOGOUS RECOMBINATION DIRECT REVERSAL DNA REPAIR DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. There are several types to repair mechanism according to the types of DNA damage.
- 3. Base Excision Repair ● Repairs damage to a single nucleotide caused by oxidation, alkylation, hydrolysis, or deamination ● Consist of DNA glycosylases and AP endonuclease ● Produce AP site during repair process
- 4. Nucleotide Excision Repair ● Repairs “bulky” lesions in DNA that alter or distort the regular DNA double helix ● Repairs Non-specific DNA damage ○ Chemical adducts ○ UV photoproducts ● Group of genes (uvr) involved in recognizing and clipping out the lesions in the DNA ● Repair is completed by DNA pol I and DNA ligase
- 5. Mismatch Repair Mechanism ● Mismatch repair (MMR) corrects errors of DNA replication and recombination that result in mispaired (but normal, that is non- damaged) nucleotides following DNA replication
- 6. Direct Repair Mechanisms: Photoreactivation by photolyase Reversal of O6 methyl Guanine to Guanine by methyltransferase
- 7. Direct repair of alkylated bases by AlkB.
- 8. Homologous recombination Resection Rad50, Mre11, Xrs2 complex Strand invasion Rad52 Rad51; BRCA2 DNA synthesis ✂ ✂✂ ✂ Ligation, branch migration, Holliday junction resolution DSB Non-homologous end-joining Ku70, Ku80 Ligation DSB DNA-PKcs Rad50, Mre11, Xrs2 complex “Cleaning up” of ends XRCC4/ Ligase IV Double Strand Breaks Repair
- 9. References Lehninger’s Principle of Biochemistry. David L, Nelson and Michael M. Cox (5th Edition) Friedberg. DNA repair and mutagenesis. ASM Press, Washington, D. C. Marti TM, Kunz, C, Fleck O. 2002 DNA mismatch repair and mutation avoidance pathways. J. Cell. Physiol. 191: 28-41 Harfe BD, Jinks-Robertson S. 2000 DNA mismatch repair and genetic instability. Annu. Rev. Genet. 34: 359-399. Krokan, HE, Standal, R, Slupphaug, G. 1997 DNA glycosylases in the base excision repair of DNA Biochem. J. 325: 1-16. De Laat, WL, Jaspers, NGJ, Hoeijmakers, JHJ. 1999 Molecular mechanism of nucleotide excision repair. Genes Dev. 13: 768-785 Petit, C, Sancar, A. 1999 Nucleotide excision repair: from E. coli to man. Biochimie 81: 15-25