Академический Документы
Профессиональный Документы
Культура Документы
consequence of telomere
dysfunction
AAAS
Annual meeting
February 19th 2010
Carol Greider
Daniel Nathans Professor
& Director Department of Molecular
Biology and Genetics
Johns Hopkins University
School of Medicine
Protect ends
Maintain length
TTGGGG
Replication
Replication
Replication
Ori
Marker
Maintain linear
plasmid in yeast
Telomerase activity
identified
Telomerase
TERT
Tissue renewal
Telomerase
is limiting in
cells
mTR+/ -
mTR+/ -
mTR- / -
G1
G1
G2
G2
G3
G3
G4
G4
G5
Cell death
or
Senescence
G5
G6
G6
mTR+/ -
mTR- / - (G1)
G1
G2
G2
G3
G3
G4
G4
G5
G5
G6
WT
KO-G2
KO-G4
KO-G6
mTR+/ -
mTR+/ -
mTR- / -
G1
G1
G2
G2
G3
G3
G4
G4
G5
Cell death
or
Senescence
G5
G6
G6
Replication
Replication
Cell Death
Cancer
Tissue renewal
Nature 2001
I1
Genetic anticipation.
Affected people are
heterozygous for hTR or
hTERT mutations.
II 1
III 1
Dominant negative or
haploinsufficiency?
mTR+/ -
HG1
HG1
HG2
HG2
HG3
HG3
HG4
HG5
HG4
Telomerase
is limiting in
cells
mTR+/ -
HG1
HG1
HG2
HG2
HG3
HG3
HG4
WT5*
HG5
HG4
KO(G5)
100
75
50
25
0
100
200
300
400
Days
mTR+/ -
HG1
HG1
HG2
HG2
HG3
HG3
HG4
WT5*
HG5
HG4
KO(G5)
HG4
KO
HG4
HG5
WT5*
SPLEEN
WEIGHT
Corrected
Spleen
Weight
7
6
5
4
3
2
1
0
wt (n=6)
wt8*1 (n=7)
ko (n=9)
mTR+/ - HG4
mTR+/ + WT5*1
mTR+/ +WT5*1
mTR+/ +WT5*2
mTR+/ +WT5*2
mTR+/ +WT5*3
mTR+/ +WT5*4
mTR+/ +WT5*3
mTR+/ +WT5*4
Telomerase is limiting in
Armanios et al. AJHG
cells
II 1
III 1
Greider Lab
Telomere length regulation
Vinny Raganathan
Sofia Vidal-Cardenas
Carla Connely
Response to telomere
dysfunction
Nini Guo
Margaret Strong
Tammy Morrish
Collaborators
Oncology
Mary Armanios
Jonathan Alder
Erin Parry
Pathology
Baktiar Karim
David Huso