Telomeres, Cell Aging and Senescence Flashcards
end replication problem
5’ end of each newly-synthesized lagging strand cannot be completed
results in shorter and shorter dna strands which can eventually cut into genes
Telomerase
the enzyme able to both maintain and extend the length of telomeres.
Protein + RNA
protein (TERT) and RNA (TERC) subunits
catalyzes the addition of telomeric repeats at the telomere
Telomerase enzyme includes the RNA
template for the
species of its origin
Telomerase is strongly expressed only in a limited
number of cells
stems cells, germline, cancer
Cyclins
promote progression through the cell cycle
- partner with CDK
P21
inhibitor of a cyclin/CDK complex that turns off cell cycle
p53
a tumor suppressor gene (delete = get a tumor)
p21 inhibitor is expressed
in senescent cells
Hayflick limit
cells have a limited ability to divide
Werner syndrome/fibroblasts
Fibroblasts Divide Fewer Times
Mitotic Clock Theory
old cells “sense” short telomeres and induce cell cycle arrest
How do shortened telomeres cause somatic cell senescence?
TF p53 is phosphorylated upon stress
-p21 is transcribed
p21 inhibits cyclin/Cdk to arrest cells
supporting mitotic clock theory
Adding telomerase gene hTRT diminishes senescence reporter b-galactosidase
- changes hayflick limit
- Mice manipulated to have extra long telomeres live longer
dyskeratosis congenita
Defects in telomerase, TERT, or telomerase RNA component, TERC