L16- Review of cell cycle

Question 1

cell cycle is exploited by

Answer 1

chemotherapy and antibiotics

Question 2

G1

Answer 2

content replication

Question 3

S

Answer 3

DNA replication

Question 4

G2

Answer 4

everything is checked

Question 5

M

Answer 5

cell division

Question 6

DNA damage response (3)

Answer 6

• permanent cell cycle arrest (G0) - DNA repair - cell death

Question 7

DNA repair mechanisms for ssDNA breaks

Answer 7

• mismatch repair - base excision repair - nucleotide excision repair

Question 8

DNA repair mechanisms for dsDNA breaks

Answer 8

• non homologs end joining - homologous recombination

Question 9

mitosis summary

Answer 9

• Cell division of somatic cells - Production of two identical daughter cells (with same chromosome content as parental cell) - 50 mitotic rounds during development - Mitotic growth necessary for some tissue (epidermis, mucosae, bone marrow, spermatogonia)

Question 10

meiosis summary

Answer 10

• Cell division of germ line cells - Production of 4 non-identical cells (half chromosome content of parental cell) - One round of replication followed by two rounds of division (meiosis I and II) - Diploid (2n) haploid (n) - Production of eggs and sperm

Question 11

the end of a linear chromosome are not readily replicated by cellular DNA polymerases. What might be a problem with producing the final Okazaki fragment on the lagging strand>

Answer 11

Right at the end of the chromosome all Okazawaki fragments accept the last one (on the laggings strand) have been made. DNA primer which binds is longer than the remaining DNA and there is not enough space for DNA primase to bind to read the DNA.  Leads to one missing Okazaki fragment- loss of telomere sequence.  If this process continues then the DNA will shorten after each replication.

Question 12

telomeres

Answer 12

short repeats of DNA at the end of chromosomes) prevent loss of genes as chromosome ends were down

Question 13

Repeats that make up a telomere are

Answer 13

eaten away slowly over many division cycles- providing a buffer that protects coding DNA.

Question 14

which enzyme prevents telomere shortening

Answer 14

telomerase

Question 15

telomerase

Answer 15

1. Telomerase binds to a special RNA molecule that contains a sequence complementary to the telomeric repeat (TTAGGG) 2. It extends the overhanging strand of the telomere DNA using complementary RNA as a template 3. When the overhand is long enough, the matching strand can be made using RNA primer and DNA polymerase 4. Production of a double-stranded DNA

Question 16

xeroderma pigments.

Answer 16

All the genes associated with the development of XR, a rare inherited conditions that predisposes individuals to a skin lesions and increased incidence of skin cancer, are involved with nucleotide excision repair. Genes associated are those relating to Nucleotide excision repair mechanism e.g. POMH

Question 17

differential sensiitvity

Answer 17

Chemotherapy kills most subclones of a tumour. Diff subclones have different sensitivity to chemotherapy. One cell line may be resistant to chemotherapy (mutated in a diff pathway) and cause regrowth of tumour

Question 18

chemotherapy-induced mutagenesis

Answer 18

Chemotherapy may kill off cancer cells, but they can also mutate other subclones of the tumour, making it more resistant or aggressive cancer cell line

Question 19

PARP inhibitors

Answer 19

• BRCA1, BRCA2 and PALB2 are proteins that are important for the repair of double-strand DNA breaks by the error-free homologous recombinational repair o When the gene for one of these proteins is mutated, the change can lead to errors in DNA repair that can eventually cause breast cancer. When subjected to enough damage at one time, the altered gene can cause the death of the cells.
• PARP1 is a protein that is important for repairing single-strand breaks o If such nicks persist unrepaired until DNA is replicated, then the replication itself can cause double strand breaks to form.
• Drugs that inhibit PARP1 cause multiple double strand breaks to form in this way

o In tumours with BRCA1, BRCA2 or PALB2 [8] mutations, these double strand breaks cannot be efficiently repaired, leading to the death of the cells.

o In normal cells that don’t replicate their DNA as often as cancer cells, and that lack any mutated BRCA1 or BRCA2 still have homologous repair operating, which allows them to survive the inhibition of PARP.

Question 20

Synthetic lethality strategies

Lots of pathways in the cell to repair damage.

Answer 20

e. g. normal cells have normal pathways for cell survival after damage e.g. gene A and Gene B. In normal cells knocking out one of these genes still leads to cell survival- one gene pathway is enough.
e. g in cancer cells: Gene A pathway may not be working and Gene B may have a cancer mutation- both genes are not working —> cell death