Lecture 6: DNA Repair And Replication Flashcards
What type of genome instability characterizes Down syndrome, klinefelter’s syndrome, patau syndrome, and triple-X syndrome?
Whole xs loss or gain Down trisomy 21 Klinefelter's XXY Patau trisomy 13 Triple X XXX
What type of genomic instability characterizes fragile X syndrome and Huntington’s disease?
Large scale repeat expansion
In what direction are phosphodiester bonds formed in replication?
5’ –> 3’
Describe conservative and dispersive models of DNA replication
Conservative: daughter DNA has two new strands
Dispersive: bits and pieces
What did the Meselson-Stahl experiment show?
DNA replication is semi-conservative
What are the four phases of interphase?
M G1 S and G2
What enzyme performs proofreading for DNA-pol, and in what direction does it work?
Exonuclease 3’ –> 5’
How do exonuclease and endonuclease differ?
Exo: chews from end, only proceeds in one direction (3 to 5), involved in DNA rep
Endo: cuts like scissors within DNA, not involved in DNA rep
Does DNA-pol have proofreading ability?
Yes - exonuclease
Which DNA repair mechanism corrects 99% of replication errors?
DNA mismatch repair
Which genes are mutated in Hereditary Non-Polyposis Colon Caner?
Mismatch repair genes
What is the phenotype called in hereditary non-Polyposis colon cancer? Which genes are mutated?
Mutator phenotype
Mismatch repair genes
Which DNA-pol family replicates chromosomes?
B
Pol alpha, gamma, epsilon
What type of replication and repair does DNA-Pol A family do?
(Pol-gamma)
Mitochondrial
In which process are DNA-PKcs, Ku, DNA ligase IV-XRCC4, Artemis, XLF, and Metnase involved?
Double stranded break repair
Defects in ATM causes which syndrome?
Ataxia telangiectasia
Mutation of BLM protein causes which syndrome?
Bloom Syndrome
What do the terms ataxia and telangiectasia mean?
Ataxia = abnormal balance Telangiectasia = dilation of blood vessels
Which syndrome has sensitivity to gamma irradiation, susceptibility to lymphomas, dilation of blood vessels in skin and eyes, and immune dysfunction?
Ataxia telangiectasia
Which syndrome has sensitivity to mild alkylating agents, susceptibility to carcinomas, leukemias, and lymphomas, and facial telangiectases?
Bloom syndrome
What is the function of BLM? What syndrome is caused by its mutation?
RecQ helicase. Replication stress response. Bloom syndrome
What is the function of ATM? What syndrome does its mutation cause?
Protein kinase in replication stress response. Upregulates p53. Ataxia telangiectasia
What do AZT, ddC, and ddI have in common?
Nucleotide analogue chain terminators
AZT - HIV
ddC and ddI - cancer
What do hydroxyurea, camptothecin, and 5-FU have in common? What do they target?
Enzyme inhibitors
Hydroxyurea- RNR (depletes deoxyribonucleotides)
Camptothecin- Top1
5-FU - thymidylate synthetase (depletes dTTP)
