Telomeres and telomerase Flashcards
what are the 3 phases of cell division
rapid cell division, division slows, division stops- senescence
what sequences are telomeres made up of
simple tandem repeats with a G rich 3’ end (TTAGGG)
what is the role of telomeres
prevent chromosomal DNA being recognised as broken to prevent DNA joining
how does telomerase prevent telomere shortening
it carries its own template RNA primer which is complementary to the telomere repeat sequence. the primer allows end replication by DNA polymerase activity
what is the RNA component of telomerase called
hTERC
what is the result of non-functional telomerase in tetrahymena
cells rapidly lost viability and became apoptotic (they are normally immortal).
which cells is telomerase active in eukaryotes
germ cells, stem cells and certain white blood cells
is it possible to make human cells immortal
yes- human fibroblasts were transfected with TERT (protein component of telomerase) and found these cells had extended/limitless lifespan but were not oncogenic
how is hTERT negatively regulated during development
Menin, TGFb and mad1- 3 tumour suppressor pathways
which gene was found to activate hTERT
hSIRT2
what are TRF1 and 2
multiprotein complexes which bind to telomeres and prevent access of telomerase
how does T-loop formation regulate telomerase activity
G folds back and anneals with double stranded region of TTAGGG repeats which restricts telomerase biding
how does POT1 regulate telomerase activity
it binds at 3’ lagging strand tail and prevents telomerase binding as it inhibits base alignment between DNA and RNa template
which diseases are linked to short telomeres
cancer, pulmonary fibrosis, cardiovascular diseases, dementia, osteoporosis, diabetes, obesity, insulin resistance, werners syndrome
what is werners syndrome AKA
adult progeria
what are the symptoms of werners syndrome
skin changes, cataracts, premature atherosclerosis
what is the cause of werners syndrome
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
how can the werners syndrome phenotype in mouse model dermal fibroblasts be reversed
telomerase expression
how is cancer linked to telomere length
before becoming oncogenic they have short telomeres due to normal activity, then telomerase is reactivated rescuing telomeres but only to a specific, short length
how can telomerase activity in cancer cells be exploited in therapeutics
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
aside from genetic factors, what can cause telomere shortening
stress, smoking and drinking
