TY - JOUR
T1 - Telomerase and differentiation in multicellular organisms
T2 - Turn it off, turn it on, and turn it off again
AU - Forsyth, Nicholas R.
AU - Wright, Woodring E.
AU - Shay, Jerry W.
N1 - Funding Information:
Acknowledgements Supported in part by Department of Defense Grant DAMD17-01-1-0420 (NRF). JWS is an Ellison Medical Foundation Senior Scholar. JWS and WEW are co-holders of the Southland Financial Corporation Distinguished Chair in Geriatric Research. Centromere and telomere probes were kindly provided by Dr. Sergei Gryaznov (Geron Corporation, Menlo Park, CA).
PY - 2002/1
Y1 - 2002/1
N2 - Telomerase is a ribonucleoprotein complex that catalyses the addition of TTAGGG repeats onto telomeres, repetitive DNA structures found at the ends of linear chromosomes. The majority of human somatic tissues do not display telomerase activity and undergo telomeric shortening with consecutive divisions. This telomeric shortening results in replicative senescence in vitro and likely in vivo. Telomerase activity is present in the vast majority of tumors, preventing telomeric shortening and thereby enabling indefinite cell divisions. Telomerase activity is regulated throughout human development, undergoing silencing in almost all organ systems from embryogenesis onwards. However, regulated telomerase activity is seen in basal/stem cell compartments of highly regenerative tissues, such as those of the immune system, skin, and intestine. Avian species display telomerase repression and telomeric shortening similar to that seen in humans. However, rodents retain telomerase-competency throughout their lifespan and have not been shown to display division-dependent telomere shortening. The regulation of telomerase activity in plants is less well understood, although early indications suggest ubiquitous competency. The aim of this review is to present current data regarding developmental regulation of telomerase in humans, mice, chickens and flowering plants. Differentiation, quiescence and telomerase activity regulation will then be addressed in three human representative tissue systems; blood, skin, and intestine. We will also highlight similarities, differences and misconceptions in the developing field of telomere and telomerase biology.
AB - Telomerase is a ribonucleoprotein complex that catalyses the addition of TTAGGG repeats onto telomeres, repetitive DNA structures found at the ends of linear chromosomes. The majority of human somatic tissues do not display telomerase activity and undergo telomeric shortening with consecutive divisions. This telomeric shortening results in replicative senescence in vitro and likely in vivo. Telomerase activity is present in the vast majority of tumors, preventing telomeric shortening and thereby enabling indefinite cell divisions. Telomerase activity is regulated throughout human development, undergoing silencing in almost all organ systems from embryogenesis onwards. However, regulated telomerase activity is seen in basal/stem cell compartments of highly regenerative tissues, such as those of the immune system, skin, and intestine. Avian species display telomerase repression and telomeric shortening similar to that seen in humans. However, rodents retain telomerase-competency throughout their lifespan and have not been shown to display division-dependent telomere shortening. The regulation of telomerase activity in plants is less well understood, although early indications suggest ubiquitous competency. The aim of this review is to present current data regarding developmental regulation of telomerase in humans, mice, chickens and flowering plants. Differentiation, quiescence and telomerase activity regulation will then be addressed in three human representative tissue systems; blood, skin, and intestine. We will also highlight similarities, differences and misconceptions in the developing field of telomere and telomerase biology.
KW - Development
KW - Differentiation
KW - Telomerase
KW - Telomere
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U2 - 10.1046/j.1432-0436.2002.690412.x
DO - 10.1046/j.1432-0436.2002.690412.x
M3 - Review article
C2 - 11841477
AN - SCOPUS:0036362266
SN - 0301-4681
VL - 69
SP - 188
EP - 197
JO - Differentiation
JF - Differentiation
IS - 4-5
ER -