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30 Cards in this Set

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In humans, each cell normally contains __ pairs of chromosomes, fora total of ___.

23 pairs of chromsomes = 46



What are two ways the loss ofheterozygosity can occur?

When people inherent adamaged allele of a tumorsuppressor gene: the loss orinactivation of the normalallele




Mis-segregation duringmitosis, also called nondisjunction

What happens during mis-segregation?

one daughter cellgets three copies of achromosome and the othergets one.




Overtime, the extra chromosomeis lost which creates a cellwith homozygous mutantalleles.

What happens during mitoticrecombination?

recombination between homologous chromatids during mitosis




can become homozygous for a mutant allele



What is E2F needed for?

activator of transcription of proteins needed for DNA synthesis

What does unphosphorylated Rb do?

binds to E2F



represses transcription


What happens when Rb is phosphorylated?

DNA replication

What protein phosphorylates Rb?

CdcD/CDK4

What protein is needed for CDK4activation?

Cyclin D

What protein blocks CycD activation ofCDK4?

p16




leads to G1 arrest

In sum, what is the normal role of Rb?




If disrupted?

represses transcription




if disrupted, E2F can undergo cell cycle into S phase

What would occur if CdcD activity iselevated?




If p16 is disrupted?

Phosphorylation of Rb and over activation of E2F transcription factor




continual active CdcD unit

What does the HPV protein E7 do?

inhibits Rb so it cannot bind and repress E2F

Carcinogen

agent that causes cancer




can be chemicals, viruses, hormones, ionizing radiation, or solid materials




can be natural OR man-made




2 types of chemical carcinogens: direct & indirect acting



Direct acting carcinogens

rare chemical mutagens




are mainly reactiveelectrophiles that are able to directly react with thenitrogen and oxygen atoms in DNA




ethyl methane sulfonate (EMS)


dimethyl sulfate (DMS)

Indirect-acting carcinogens

typically unreactive and water insoluble




The problem is that the addition of the electrophiliccenters can allow these formally harmless (to DNA)molecules to damage DNA.

Where is Benzo(a)pyrene found?

a purified chemical in coal tar

What does P-450 do?

adds -OH groups to benzo(a)pyrene to make it


watersoluble.




This makes it reactive and allows it to covalently bondwith guanine in DNA.




The modified Guanine causes DNA polymerase to insertan A instead of a C opposite to the G.This error is copied forward.

What geneis commonly mutated in lung cancer?

p53

What is the normal function of p53?

Activation of p53 leads to cell cyclearrest, DNA


repair, and apoptosis

What occurs in p53 knockout mice?

an increase in the frequency of cancer.

How are heterocyclic amines produced?

cooking of muscle from beef, pork, fowl, fish at high temperatures

What enzyme converts heterocyclicamines into a form that can react with DNA?

P-450

What are the two systems that are usedto repair single base errors?

mismatch repair




and Excision repair

In the disease Xeroderma pigmentosumwhat is disrupted?

nucleotide excision repair




skin cancer at 1000x the normal rate

What can occur when double strandbreaks are repaired?

mitotic recombination or


chromosomal translocations

Telomeres

short repeatswith the sequenceTTAGGG at the ends of linear dsDNA




Telomerase carries with it aRNA template (CAAUCCCAAUC) that can bind tothe old DNA and offers aplace for POL to both bindand to extend new DNA.

What happens when telomeres are veryshort?

Short telomeres arerecognized as a typeof DNA damageand lead to p53activation andapoptosis (Bax)

Is telomere length longer or shorterthan normal in cancer cells?

longer

What happens when the telomerase geneis knocked out in mice?

lethal after a few generations