Topic 13 - DNA Repair + Cancer e667eca282dc4446945af30ff6813559.pdf

🎃 Topic 13 - DNA Repair + Cancer What is the importance of DNA + its repair DNA is the only biological macromolecule that is repaired. All others are replaced. Cancer is a consequence...

🎃 Topic 13 - DNA Repair + Cancer What is the importance of DNA + its repair DNA is the only biological macromolecule that is repaired. All others are replaced. Cancer is a consequence of inadequate DNA repair. 3 types of Excision Repair mismatch repair base excision repair nucleotide excision repair What is the DNA Mismatch Repair’s Basic Concept Topic 13 - DNA Repair + Cancer 1  What is the main enzyme used in DNA Base excision Repair DNA Glycolysaes detect and replace bases How does DNA Base excision repair work specifically Removal of the incorrect base by an appropriate DNA N-glycosylase to create an AP site. An AP endonuclease nicks on the 5' side of the AP site to generate a 3'-OH terminus. Extension of the 3'-OH terminus by a DNA polymerase to repair the strand Topic 13 - DNA Repair + Cancer 2  What is the relationship between Base Excision Repair and Human Disease Many cancers have mutations in BER genes. Links to cognition: DNA methylation and demethylation required for memory formation and maintenance. demethylation of specific genes dependent on BER How does nucleotide excision repair work in general terms? Damage recognition causes binding of a multi-protein complex at the damaged site Double incision of the damaged strand several nucleotides away from the damaged site, on both the 5' and 3' sides Removal of the damage-containing oligonucleotide Filling in of the resulting gap by a DNA polymerase + Ligation What are the 2 types of nucleotide excision repair Transcription Coupled Repair - transcription only Global Genomic Repair - happens to DNA at anytime Explain how Transcription Coupled Repair Works Topic 13 - DNA Repair + Cancer 3  specific mechanism of nucleotide excision repair (NER) that primarily targets and repairs DNA damage that obstructs the progress of RNA polymerase during transcription. helps maintain the integrity of actively transcribed genes by promptly repairing lesions that would otherwise impede transcription. 1. Detection of Damage: During transcription, RNA polymerase encounters a DNA lesion that blocks its progress. 2. Recruitment of Repair Factors: When the blockage is detected, specialized proteins are recruited to the site of damage and verify the damage 3. DNA Unwinding: The damaged DNA strand is locally unwound, allowing access to the damaged DNA for repair enzymes. 4. Excision and Repair: specific remove the damaged DNA strand, creating a gap. DNA polymerases and ligases then fill in the gap with new, undamaged DNA nucleotides. 5. Resumption of Transcription: gene can continue to be transcribed without being hindered by the DNA damage. What is Complementation? complementation = the ability of two mutants in combination to restore a normal phenotype. Complementation also refers to a relationship between two different strains of an organism which both have homozygous recessive mutations that produce the same phenotype but which do not reside on the same (homologous) gene. What does cancer require in order to propagate Cancer requires accumulation of mutations in cells capable of propagating. What is Bloom’s Syndrome Helicase Deficiency autosomal recessive short stature; a sun-sensitive, red rash that occurs primarily over the nose and cheeks; mild immune deficiency Topic 13 - DNA Repair + Cancer 4  2 methods of Double-Strand Break Repair homologous recombination Non-homologous end joining (NHEJ) What is Homologous Recombination for DNA repair Homologous Recombination is Based on the Ability of Single DNA Strands to Find Regions of Near-Perfect Homology (Genes) Elsewhere in the Genome How does Non-homologous End Joining repair work (NHEJ) 1. Detection of DNA Damage: cell recognizes DNA damage break 2. End Processing: The broken DNA ends are often uneven, may have damaged/missing nucleotides. NHEJ begins by trimming/modifying these broken ends to make them more compatible for rejoining. Topic 13 - DNA Repair + Cancer 5  3. Binding of NHEJ Proteins: Specialized proteins involved in NHEJ, such as Ku70/Ku80, bind to the ends of the broken DNA to protect them and keep them in close proximity. 4. Ligation: DNA ligase joins the processed ends of the DNA strands together, even if the ends are not perfectly complementary. Results in the loss or addition of a few nucleotides at the repair junction, which may lead to small insertions or deletions in the repaired DNA. 5. Completion of Repair: DNA ends are joined, the double-strand break is repaired, and the DNA molecule is made continuous again.. One advantage of NHEJ - Non-homologous End Joining repair relatively quick and efficient DNA repair mechanism One disadvantage of NHEJ - Non-homologous End Joining repair may introduce mutations due to its error-prone nature Topic 13 - DNA Repair + Cancer 6