Telomeres and telomerase

Question 1

what are the 3 phases of cell division

Answer 1

rapid cell division, division slows, division stops- senescence

Question 2

what sequences are telomeres made up of

Answer 2

simple tandem repeats with a G rich 3’ end (TTAGGG)

Question 3

what is the role of telomeres

Answer 3

prevent chromosomal DNA being recognised as broken to prevent DNA joining

Question 4

how does telomerase prevent telomere shortening

Answer 4

it carries its own template RNA primer which is complementary to the telomere repeat sequence. the primer allows end replication by DNA polymerase activity

Question 5

what is the RNA component of telomerase called

Answer 5

hTERC

Question 6

what is the result of non-functional telomerase in tetrahymena

Answer 6

cells rapidly lost viability and became apoptotic (they are normally immortal).

Question 7

which cells is telomerase active in eukaryotes

Answer 7

germ cells, stem cells and certain white blood cells

Question 8

is it possible to make human cells immortal

Answer 8

yes- human fibroblasts were transfected with TERT (protein component of telomerase) and found these cells had extended/limitless lifespan but were not oncogenic

Question 9

how is hTERT negatively regulated during development

Answer 9

Menin, TGFb and mad1- 3 tumour suppressor pathways

Question 10

which gene was found to activate hTERT

Answer 10

hSIRT2

Question 11

what are TRF1 and 2

Answer 11

multiprotein complexes which bind to telomeres and prevent access of telomerase

Question 12

how does T-loop formation regulate telomerase activity

Answer 12

G folds back and anneals with double stranded region of TTAGGG repeats which restricts telomerase biding

Question 13

how does POT1 regulate telomerase activity

Answer 13

it binds at 3’ lagging strand tail and prevents telomerase binding as it inhibits base alignment between DNA and RNa template

Question 14

which diseases are linked to short telomeres

Answer 14

cancer, pulmonary fibrosis, cardiovascular diseases, dementia, osteoporosis, diabetes, obesity, insulin resistance, werners syndrome

Question 15

what is werners syndrome AKA

Answer 15

adult progeria

Question 16

what are the symptoms of werners syndrome

Answer 16

skin changes, cataracts, premature atherosclerosis

Question 17

what is the cause of werners syndrome

Answer 17

altered levels of WRN which is part of TRF2 complex which regulates telomerase activity. loss of WRN causes deletion of telomeres and cells with a lower hay flicks limit

Question 18

how can the werners syndrome phenotype in mouse model dermal fibroblasts be reversed

Answer 18

telomerase expression

Question 19

how is cancer linked to telomere length

Answer 19

before becoming oncogenic they have short telomeres due to normal activity, then telomerase is reactivated rescuing telomeres but only to a specific, short length

Question 20

how can telomerase activity in cancer cells be exploited in therapeutics

Answer 20

exploit the activity to make toxic telomeric DNA using a mutant template RN- this reduced cell viability and increased apoptosis in breast and prostate cancer

Question 21

aside from genetic factors, what can cause telomere shortening

Answer 21

stress, smoking and drinking