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45 Cards in this Set
- Front
- Back
How do we know if something is a mutagen?
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Amen test
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what is ames test
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mimics what happens when animals are exposed to chemicals
- bacteria are exposed to chemicals with mamilliam liver enzyme |
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ames test procedure
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salmonella typhimurium
- these bacteria have various mutations that they cannot synthetize histidine - plated on medium lacking histine and then they count number of mutations after exposure to chemicals |
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number of revertants from His- to HIS +
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a compound is mutagenic if INCREASE in reversion rate
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Direct repair of DNA damage
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1. identify and reverse damage
- proofreading of DNA pol |
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repair of UV-induced photoproducts
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pyrimidine dimers can be repaired by:
photoreactive repair |
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photoreactive repair
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enzyme: photolyase uses visible light to break bonds between pyrimidine dimers
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which gene encodes photolyase?
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gene phr (photoreactive repair) gene
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repair damage done by alkylating agents
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enzymes remove added groups restoring base to original structure
- ex: o6-methyguanine --> guanine by enzyme --> methyltransferase --> enzyme is deactivated after one process |
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nucleotides can be removed and replaced if they cannot be repaired
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double strand acts as template
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UV repair
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a short segment surrounding DNA photoproduct can be removed
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which genes encode the enzymes to reapir UV repair
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uvr-A, uvr-B, uvr-C, uvr-
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process of UV repair
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2 uvr-A + 1 uvr-B bind to strand opposite photoproduct
* uvr-A leaves uvr-C joins uvr-B to form a cleaving complex that cleaves phosphodiester bonds on either side of photoproduct uvr-D(helicase) + dna pol 1 bind and fill in missing nucleotides |
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nucleotide exicision repair
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dna glycolysase remove modified purine base leaving an apurinic site
- AP nuclease removes the remainder of the nucleotide - dna pol + dna ligase fill in gap |
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dna damage signalling system
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active throughout cell cycle - looking for damage
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key molecules in damage signalling system
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ATM (kinase) phosphorylates p53 repair pathway
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p53 controls
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1. pause of cell cycle by G1-S
2. apoptosis |
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what are levels of p53 in healthy cell
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they are low
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what happens to p53 when a damage is notified
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the levels increases and two possible pathways:
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two pathways of p53
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1. pause in cell cycle to repair damage
--> when p5 increases due to increase in ATM then initiates cell pause in G1 becayse p21 increases and inhibits the formation of cyclin-CDK |
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cyclin-CDK
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?? what does this do?
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2. apoptosis and p53
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p53 activates transcription of BAX gene which encodes slow acting inhibitor BCL2
- BCL2 represses apoptosis but when damage cell: -- the formation of BAX causes BCl2 to bind to BAX and therefore allows the cell to go to apoptosis |
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BCL2
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inhibits apoptosis
when in presence of BAX gene it binds to it and therefore cell goes to apoptosis |
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p21
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cyclin-CDK inhibitor
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mutation in DNA damage repair genes
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Li-fraumeni syndrome - mutation in p53 repair pathway
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nondisjunction
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homologs and sister chromatids do not separate properly
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euploidy
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normal number of chromosome pairs
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aneuploidy
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abnormal number of chromosome pairs
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nondisjuction in germ-line cells
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anueploid gametes: one daughter cell (n+1)one daughter cell (n-1) fusion of these with normal gametes (anueploid zygotes) (2n+1) trisomic (2n-1) monosomic |
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nondisjunction in meiosis II
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failure of sister chromatids of 4 gametes produced: 2 are normal 1 (n+1) --> + n = zygote (2n+1) trisomic 1 (n-1) --> + n = zygote (2n-1) monosomic |
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gene balance
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change in gene dosage leads to imbalance in gene products
- most animals are highly sensitive - plants are not affected |
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anueploidy in humans
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autosomal chromosomes
only trisomics 13,18,21 are observed monosmies: not observied multiple sex-chromosome anueploids are observed both trisomies and monosmies survive on sex-chromosome |
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trisomies of autosomal chromosomes
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13,18,21
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trisomies and monosomies of sex chromosomes
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47 xxy47 xyy47 xxx45 xo
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autosomal trisomy 13
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patau
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autsomal trisomy 18
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edward
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autosomal trisomy 21
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down syndrome
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trisomy 21 - down syndrome
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a small number of genes on chromosome 21 are linked to abnormalities
- DSCR DYRK |
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DSCR
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down syndrome critical region
where gene: DYRK known to produce similiar symptoms in mice |
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sex trisomies and monosomies
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47 xxy (kla?)
47 xyy (jacob syndrome) 47 xxx (triple x?) 45 xo (turner syndrome) |
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turner syndrome
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45 XO
SHOX gene is insufficient to direct normal development haploinsufficiency of this gene plays a central role in producing the symptoms of this syndrome |
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in trisomies
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meiosis results in two chromosomes going to one pole
1 chromosome going to other pole -- half gametes will be normal half will be aneuploidy -- those that are aneuoploidy are unlikely to survive --> semiinfertility of aneuiploidy |
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mosaicism
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result of mitotic nondisjunction early in embryo
- turner syndrome causes occur in females that are mosaic some 45XO, some 46 XX some have 47 XXX |
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how does mosaicism occur
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46 xx zygote - mitosis : 46 + 46
46a = normal 46b = mitotic nondisjunction --? 45 + 47 |
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l
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k
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