(History of telomeres: McClintock (1932))
Chromosome ends do not fuse —> have distincs properties that prevent fusing
“broken ends” can “heal”
only in young plant embryos after first zygotic division
(History of telomeres: Hayflick limit = end replication problem?)
(History of telomeres: telomer sequence)
made up of tandem repeats
(History of telomeres: are telomeres essential?)
History of telomeres: summary
Telomerase - working principle
Telomere length dynamics
Replicative senescence
telomeres are dsDNA + proteins —> complex = shelterin
shelterin promotes loop structure —> “t-loop”
if shelterin is dysfunctional, chromosomes fuse
because of DDR (dysfunctional telomeres)
causes senescence
DDR in telomeres
Why do telomeres shorten at all?
Regulation of telomere length
Telomeres and lifespan
lifespan does not correlate with telomere length
lifespan does correlate with shortening rate of telomeres
Telomere-related disease
Genetic anticipation
Why do gene mutations lead to short telomeres?
protein complexes cannot form
telomere RNA gets degraded
Therapeutic possibilities
Telomerase manipulation & aging/cancer
TERRA
telomeres get transcribed —> TElomeric Repeat-containing RNA —> TERRA
accumulates at short telomeres
doesnt get degraded because of lack of proteins that are encoded in long telomere
slows down telomere shortening
promotes HDR by hybridizing to DNA
delays senescence
Zuletzt geändertvor 2 Jahren
