Genetics Unit 12: Eukaryotic Cell Cycle

Front 1

Cyclin

Back 1

Regulatory protein that reulates a cells entering S phase and entering mitosis. Binds to and activates Cdk which phosphorylates things.

Front 2

What does Cdk phosphorlyation in G2 result in?

Back 2

1) Phosphorylation of lamins causing nuclear envelope breakdown.
2) Phosphorylation of microtubules leading to formation of mitotic spindle.
3) Phosphorylation of histone H1 which causes chromosome condensation
4) activation of an enzyme which degrades cyclin.

Front 3

p53

Back 3

Tumor supressor gene that is found mutated in more than 50% of breast cancer cases.

Front 4

growth factors

Back 4

Usually act through cell surface receptors to stimulate cell proliferation during development and wound healing.

Front 5

What is the mechanism by which DNA damage stops cell cycle progression?

Back 5

P53 becomes stabalized > p53 induces p21 protein which inhibits cyclin cdk comples > cell wont progress through the cell cycle till the DNA is repaired.

Front 6

Ataxia Telangiectasia

Back 6

Dont effectively block cell cycle during DNA damage. Have increased incidence of cancer b/c DNA will break and then recombine > abnormal chromosome rearrangements. Have immunodeficiency b/c lymphocytes work via DNA rearrangements. If cell cycle proceeds before the DNA is back together, cell wont work.

Front 7

Telomerase

Back 7

Enzyme which adds TTAGGG to the end of eukaryotic DNA. Compensates for the loss of sequence that occurs during each replication cycle b/c the ends cannot be replicated.
Functions via reverse transcriptase (transcribes DNA from RNA).

Front 8

Telomeres

Back 8

Ends of linear DNA. Do not stop the cell cycle and prevent dna ends from connecting to one another. However, cannot be normally replicated b/c they are at the end.

Front 9

What cells have telomerases?

Back 9

Germline cells have telomerases and maintain telomere length throughout life.
Stem cells have telomerase activity but it is lost as daughter cells differentiate.
Normal somatic cells do not have telomerases and telomeric DNA is lost during lifespan of cell.

Front 10

TERC

Back 10

RNA component of telomerase.

Front 11

Dyskeratosis congenita

Back 11

Autosomal dominant disease associated with dramatically shorter telomeres b/c of a mutation in genes that encode for telomerase components.
Symptoms arise in young adult hood. Mortality is usually from bone marrow failure though there are other problems in the skin, hair, epithelia, and lung tissue. Affected cells are stem cells with high cell turnover.

Front 12

Senescence

Back 12

Cell Aging

Front 13

Telomerase and cancer

Back 13

Many tumor cells have telomerases and can divide indefinitely. They also have full length telomeres. This may be key to the cells immortality and telomerase could be a target for chemotherapy.

Front 14

Retroviruses

Back 14

Have RNA instead of DNA. Create a double stranded DNA via their RNA template and a reverse transcriptase which creates the DNA. Viral enzymes then combine the viral dna with the host dna.

Front 15

Acyclovir

Back 15

Antiviral drug. Is a structural analog of deoxyguanosine which, when incoorperated, blocks elongation. However, can only be phosphorylated and incorporated by herpesvirus thymidine kinase.

Front 16

AZT and dideoxynucleosides

Back 16

Nucleosides which lack a 3' OH. Can be phosphorylated into neucleotides and incorporated during DNA replication where they cause premature chain termination. retroviral reverse transcriptase has a higher affinity for these analogs than normal nucleotides.

Front 17

Tenofovir disoproxil fumarate

Back 17

An anti viral drug which gets converted to tenofovir diphosphate. This competes with normal substrate for HIV reverse transcriptase. Incorporation leads to chain termination. Dosent really effect mamalian or mitochondrial DNA

Front 18

Abacavir

Back 18

Neucleoside analog used to treat HIV. Is always used in combination with other anti-retroviral agents. Is well tolerated but main side effect can be a potentially fatal hypersensitivity.

Front 19

Camptothecin

Back 19

Anti-tumor drug. Inhibits DNA synthesis by trapping covalent DNA-topoisoemrase I intermediate, blocking advancement of replication fork. Tumor cells have comsiderably more Topo 1 than reg cells.

Front 20

Anti-topo II drugs

Back 20

Anti tumor drugs, cause DNA breakage by trapping topo II DNA covalent intermediate.