Origins of Mutations and DNA Replication/Repair Flashcards
Name three common DNA lesions
Depurination (lost of purines)
Deamination (most common is cytosine to uracil)
Pyrimidine Dimers (dimerization of thymine)
What kind of mutations have variations in nucleotide sequence that might be as small as a single base pair change
Gene Mutation
- rare event (10^-10)
What kinds of mutations have rearrangements, deletions, or duplications of chromosomal regions?
chromosomal mutation
- more often than gene mutations, not still not very frequent (6x10^-4)
What kind of mutations have surplus or loss of chromosomes
genomic mutation
- most frequent type of mutations (10^-2)
What kind of mutations change methylation of DNA or in the modification of histone proteins that contribut to control of gene expression?
mutations that impact chromatin
What are point mutations?
exchange of one nucleotide for another
What are the four types of point mutations?
1) silent
2) missense
3) nonsense
4) RNA processing mutant
Which type of point mutation is this?
change in nucleotide sequence that changes the amino acid sequence
missense
Which type of point mutation is this?
change in nucleotide sequence that does not affect the resulting amino acid sequence
silent
Which type of point mutation is this?
change in nucleotide sequence that results in generation of a stop codon
nonsense
What does RNA processing mutant affect?
RNA splicing
What are the three processes that can lead to small insertions or deletions?
1) incorrect recombination
2) strand slippage during replication
3) intercalating agents
What’s incorrect recombination?
misalignment during MEIOSIS that leads to unequal crossover causing insertions or deletions of genetic material
- usually occur when there’s repetitive sequence
What is strand slippage?
occurs during REPLICATION, usually with repetitive sequence as well
- newly synthesized DNA strand may loop out in a single-stranded form. the piece slips back along the template strand. the next of replication will have a repeated sequence
What kind of mutation is this? What can result?
occurs when an insertion or deletion of nucleotides that is not a multiple of three, affects codon structure downstream of the mutation
frameshift mutations
- completely different protein product
What process is a major source of chromosomal and genome mutations?
meiosis
What process leads to recombination of genetic material leading to new combinations?
meiotic crossover
What is the process that forms haploid germ cells?
meiosis
In which phase of meiosis do chromosomes condense and is visible by light microscope?
prophase
In which phase of meiosis do chromosomes position themselves at the equator of the cell?
metaphase
What is non-disjunction?
incomplete separation of chromosomes in anaphase
- source of genetic disease
- leads to surplus or missing chromosomes in germ cells
In which chromosomes are trisomy observed? What are the names of the diseases associated with each of them?
Patau - 13
Edward - 18
Down - 21
What are the six types of DNA repair strategies employed by the cell?
1) proofreading activity of DNA Pol
2) strand-directed mismatch repair
3) base excision repair
4) nucleotide excision repair
5) non-homologous end-joining
6) homologous end-joining
Which type of DNA repair strategy is this?
A glycosylase removes the base, leaving the sugar-phosphate backbone intact. AP endonuclease then recognizes that a base is missing and cuts the sugar-phosphate backbone on one side of the missing base. Then DNA phosphodiesterase removes the deoxyribose phosphate group and DNA polyermerase and DNA ligase fills the gap.
Base excision repair
- there are different glycosylases that recognize different types of damaged bases
- most common is replacing uracil back with cytosine (deamination)
Which type of DNA repair strategy is this?
DNA repair enzymes recognize distortions and remove the incorrect base pair and ‘chew back’ the DNA to the nearest nick
strand-directed mismatch repair
Which type of DNA repair strategy is this?
once a distortion is detected, a helicase seperates the two strands and the phosphodiester backbone of the defective strand is cut on either side of the lesion. The gap is filled by DNA polymerase and DNA ligase
nucleotide excision repair
Defect in which DNA repair mechanism causes HNPCC or Lynch syndrome?
strand-directed mismatch repair
Defects in which DNA repair mechanism results in xeroderma pigmentosum?
nucleotide excision repair
Which type of end-joining repair do not result in loss of nucleotides?
homologous end-joining
- uses recombination process to repair, this is possible because somatic cells are diploid
Which type of end-joining result in loss of nucleotides leading to permanent changes?
non-homologous end-joining
- double-strand break and the two ends are joined together (no matching of base pairs at all)
What chemotherapeutic agent is often used in treatment of Hodgkin’s lymphoma?
- it’s a pro-drug that is converted to phosphoramide mustard in the liver, which is a intercalating agent
Cyclophosphamide
What chemotherapeutic agent is an analogue of cytidine that contains arabinose in place of ribose?
- the active form competes with dexoynucleotides for binding to DNA Pol thus DNA replication and repair are blocked
cytarabine
