DNA repair.pptVIP

* * * * Chapter 12 DNA Replication, Repair, and Recombination New Lodish et al. 5th Edition: Chapter 23, pages 956-969 12.4 DNA damage and repair and their role in carcinogenesis A DNA sequence can be changed by copying errors introduced by DNA polymerase during replication and by environmental agents such as chemical mutagens or radiation If uncorrected, such changes may interfere with the ability of the cell to function DNA damage can be repaired by several mechanisms All carcinogens cause changes in the DNA sequence and thus DNA damage and repair are important aspects in the development of cancer Prokaryotic and eukaryotic DNA-repair systems are analogous 12.4 General types of DNA damage and causes 12.4 Proofreading by DNA polymerase corrects copying errors Figure 12-20 DNA polymerase d 12.4 Schematic model of the proofreading function of DNA polymerase Figure 12-21 E. coli: DNA polymerases introduce about 1 incorrect base/104 polymerized nucleotides Rate of mutation is much lower: 1 mistake/109 nucleotides This is because of efficient proofreading activity All 3 DNA polymerases in E. coli have the proofreading activity In eukaryotes only d and e have the proofreading activity 12.4 Chemical carcinogens react with DNA directly or after activation, and the carcinogenic effect of a chemical correlates with its mutagenicity Figure 12-22 8.1 Induction of point mutations by EMS Figure 8-6 Scientists may induce mutations in experimental organisms by treatment with chemical mutagens (e.g, EMS) or exposure to ionizing radiation 12.4 Base deamination leads to the formation of a spontaneous point mutation Figure 12-23 Repair mechanisms can be divided into three major categories Mismatch repair: occurs immediately after DNA synthesis, uses the parental strand as a template to correct an incorrect nucleotide incorporated into the newly replicated strand. Excision repair: Removal of damaged region by specialized nuclease systems and then DNA synthesis to fill the gap. Rep