Genetics Exam 3 - Lecture 16

Front 1

How do we know if something is a mutagen?

Back 1

Amen test

Front 2

what is ames test

Back 2

mimics what happens when animals are exposed to chemicals

- bacteria are exposed to chemicals with mamilliam liver enzyme

Front 3

ames test procedure

Back 3

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

Front 4

number of revertants from His- to HIS +

Back 4

a compound is mutagenic if INCREASE in reversion rate

Front 5

Direct repair of DNA damage

Back 5

1. identify and reverse damage

- proofreading of DNA pol

Front 6

repair of UV-induced photoproducts

Back 6

pyrimidine dimers can be repaired by:

photoreactive repair

Front 7

photoreactive repair

Back 7

enzyme: photolyase uses visible light to break bonds between pyrimidine dimers

Front 8

which gene encodes photolyase?

Back 8

gene phr (photoreactive repair) gene

Front 9

repair damage done by alkylating agents

Back 9

enzymes remove added groups restoring base to original structure

- ex: o6-methyguanine --> guanine by enzyme

--> methyltransferase

--> enzyme is deactivated after one process

Front 10

nucleotides can be removed and replaced if they cannot be repaired

Back 10

double strand acts as template

Front 11

UV repair

Back 11

a short segment surrounding DNA photoproduct can be removed

Front 12

which genes encode the enzymes to reapir UV repair

Back 12

uvr-A, uvr-B, uvr-C, uvr-

Front 13

process of UV repair

Back 13

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

Front 14

nucleotide exicision repair

Back 14

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

Front 15

dna damage signalling system

Back 15

active throughout cell cycle - looking for damage

Front 16

key molecules in damage signalling system

Back 16

ATM (kinase) phosphorylates p53 repair pathway

Front 17

p53 controls

Back 17

1. pause of cell cycle by G1-S

2. apoptosis

Front 18

what are levels of p53 in healthy cell

Back 18

they are low

Front 19

what happens to p53 when a damage is notified

Back 19

the levels increases and two possible pathways:

Front 20

two pathways of p53

Back 20

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

Front 21

cyclin-CDK

Back 21

?? what does this do?

Front 22

2. apoptosis and p53

Back 22

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

Front 23

BCL2

Back 23

inhibits apoptosis

when in presence of BAX gene it binds to it and therefore cell goes to apoptosis

Front 24

p21

Back 24

cyclin-CDK inhibitor

Front 25

mutation in DNA damage repair genes

Back 25

Li-fraumeni syndrome - mutation in p53 repair pathway

Front 26

nondisjunction

Back 26

homologs and sister chromatids do not separate properly

Front 27

euploidy

Back 27

normal number of chromosome pairs

Front 28

aneuploidy

Back 28

abnormal number of chromosome pairs

Front 29

nondisjuction in germ-line cells

Back 29

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

Front 30

nondisjunction in meiosis II

Back 30

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

Front 31

gene balance

Back 31

change in gene dosage leads to imbalance in gene products

- most animals are highly sensitive

- plants are not affected

Front 32

anueploidy in humans

Back 32

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

Front 33

trisomies of autosomal chromosomes

Back 33

13,18,21

Front 34

trisomies and monosomies of sex chromosomes

Back 34

47 xxy47 xyy47 xxx45 xo

Front 35

autosomal trisomy 13

Back 35

patau

Front 36

autsomal trisomy 18

Back 36

edward

Front 37

autosomal trisomy 21

Back 37

down syndrome

Front 38

trisomy 21 - down syndrome

Back 38

a small number of genes on chromosome 21 are linked to abnormalities

- DSCR

DYRK

Front 39

DSCR

Back 39

down syndrome critical region

where gene: DYRK known to produce similiar symptoms in mice

Front 40

sex trisomies and monosomies

Back 40

47 xxy (kla?)

47 xyy (jacob syndrome)

47 xxx (triple x?)

45 xo (turner syndrome)

Front 41

turner syndrome

Back 41

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

Front 42

in trisomies

Back 42

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

Front 43

mosaicism

Back 43

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

Front 44

how does mosaicism occur

Back 44

46 xx zygote - mitosis : 46 + 46

46a = normal

46b = mitotic nondisjunction --? 45 + 47

Front 45

l

Back 45

k