Lecture 20 Flashcards
Explain the significance/function of alkylating agents
Donate methyl and ethyl groups (ethylmethylsulfonate, EMS; mustard gas);
Explain the significance/function of ionizing radiation
Dislodges electrons in tissue causing free radicals which often damages DNA
Explain the significance/function of UV radiation
UV light induces the formation of pyrimidine dimers; two thymine bases covalently bonded that blocks replication
What is the SOS pathway?
SOS system allows bacteria cells to bypass the replication block with a mutation-prone pathway
Explain the Ames test
Uses bacteria that can’t synthesize histidine due to enzyme inactivation caused by a frameshift or point mutation that substitutes an inactivating AA; they are exposed to a potential mutagen and placed on histidine-free media; number of resulting colonies reflects the mutagenicity (and maybe carcinogenicity) of the substance due to reverse mutation
Basic concept of mismatch repair and what happens when this fails (slide 18-19)
Mismatched base is added to new strand in DNA replication; exonucleases remove nucleotides on the new strand between the GATC sequence and the mismatch; DNA polymerases then replaces the nucleotides, correcting the mismatch
When it fails, can lead to cancers
Basic concept of direct repair and what happens when this fails (slide 20)
Repairs pyrimidine alkylation, simply removing the unwanted methyl group and restoring the normal guanine structure (usually occurs in guanines)
When it fails, can lead to increased risk of cancer; methylation is often associated with the inactivation of genes
Basic concept of base-excision repair and what happens when this fails (slide 21)
Excises modified bases and then replaces one or more nucleotides with the correct original sequence
When it fails = cancer
Basic concept of nucleotide-excision repair and what happens when this fails (slide 22-23)
Removes bulky DNA lesions, like pyrimidine dimers, that distort the double helix; distortion is cut out and polymerase and ligase restore the original sequence; also responsible for T-T dimer repair
Cancer
Basic concept of nonhomologous end joining and what happens when this fails (slide 24)
Repairs double stranded breaks, but the ends are not joined back together properly
Can lead to several syndromes, including Severe Combined ImmunoDeficiency (SCID)
Basic concept of homologous recombination and what happens when this fails (slide 24)
Repairs double stranded breaks; requires homologous section of DNA to act as a template for repair of the damaged/broken fragment; more accurate than NHEJ because of the template
Basic concept of translesional polymerases and what happens when this fails (slide 25)
Allow polymerases to skip over distortions/dimers but often results in mutations; just does its best to bypass the mutation and keep replication going
What kinds of mutations are most often created by UV radiation?
T-T dimers that will block replication of the DNA
What’s the difference between spontaneous and induced mutations?
Spontaneous occur just in nature/naturally in an organisms life; induced mutations are done on purpose usually in the lab to study phenotypic outcomes
What is bloom syndrome?
Autosomal recessive disorder characterized by disproportionate pre- and postnatal growth deficiency; sun-sensitivity, telangiectactic, hypo- and hyperpigmented skin; predisposition to malignancy and chromosomal instability
What is Xeroderma pigmentosa?
Autosomal recessive disease; abnormal skin pigmentation and acute sensitivity to sunlight; strong predisposition to skin cancer; sunlight exposure produces pyrimidine dimers in skin cell DNA which can’t be repaired; cells usually defective in nucleotide excision repair; incidence is 1:250,000
What is cockayne syndrome and trichothiodystrophy
Results from mutations in some of the same genes that cause xeroderma pigmentosum; no increased risk of cancer, but multiple developmental and neurological problems; incidence is 1:250,000 in US and 1:40,000 in Japan
What is hereditary nonpolyposis colon cancer?
Responsible for about 15% colon cancers; arises from mutations in proteins that carry out mismatch-repair processes
