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PRESS RELEASE 2009-10-05 The Nobel Assembly at Karolinska Institutet

PRESS RELEASE 2009-10-05 The Nobel Assembly at Karolinska Institutet has today decided to award The
Nobel Prize in Physiology or Medicine 2009 jointly to Elizabeth H. Blackburn,
Carol W. Greider and Jack W. Szostak

PRESS RELEASE 2009-10-05

The Nobel Assembly at Karolinska Institutet has today decided to award

The Nobel Prize in Physiology or Medicine 2009

jointly to

Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak

for the discovery of

how chromosomes are protected

by telomeres and the enzyme telomerase

SUMMARY

This year´s Nobel Prize in Physiology or Medicine is awarded to three scientists who have
solved a major problem in biology: how the chromosomes can be copied in a complete way
during cell divisions and how they are protected against degradation. The Nobel Laureates
have shown that the solution is to be found in the ends of the chromosomes the telomeres
and in an enzyme that forms them telomerase.

The long, thread-like DNA molecules that carry our genes are packed into chromosomes, the
telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that
a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol
Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere
DNA. These discoveries explained how the ends of the chromosomes are protected by the
telomeres and that they are built by telomerase.

If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere
length is maintained, and cellular senescence is delayed. This is the case in cancer cells,
which can be considered to have eternal life. Certain inherited diseases, in contrast, are
characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel
Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has
stimulated the development of new therapeutic strategies.

The mysterious telomere

The chromosomes contain our genome in their DNA molecules. As early as the 1930s, Hermann
Muller (Nobel Prize 1946) and Barbara McClintock (Nobel Prize 1983) had observed that the
structures at the ends of the chromosomes, the so-called telomeres, seemed to prevent the

Then and Now: Cancer Treatments from Henrietta Lacks to Today iv

chromosomes from attaching to each other. They suspected that the telomeres could have a
protective role, but how they operate remained an enigma.
chromosomes from attaching to each other. They suspected that the telomeres could have a
protective role, but how they operate remained an enigma.
When scientists began to understand how genes are copied, in the 1950s, another problem
presented itself. When a cell is about to divide, the DNA molecules, which contain the four bases that
When
form the scientists
genetic code,beganare to copied,
understandbase by how genes
base, by DNA are polymerase
copied, in enzymes.
the 1950s, anotherfor
However, problem
one of
presented
the two DNA itself.strands,
When aacell is aboutexists
problem to divide, the DNA
in that molecules,
the very end ofwhich the contain the fourbe
strand cannot bases that
copied.
form the genetic
Therefore, code, are copied,
the chromosomes should base by base, byevery
be shortened DNA time
polymerase enzymes.but
a cell divides However, for one
in fact that is notof
the twothe
usually DNAcasestrands,
(Fig 1). a problem exists in that the very end of the strand cannot be copied.
Therefore, the chromosomes should be shortened every time a cell divides but in fact that is not
usually the case
Both these (Fig 1).were solved when this year´s Nobel Laureates discovered how the telomere
problems
functions and found the enzyme that copies it.
Both these problems were solved when this year´s Nobel Laureates discovered how the telomere
functions
Telomere and DNAfound the the
protects enzyme that copies it.
chromosomes
In the early phase of her research career, Elizabeth Blackburn mapped DNA sequences. When
Telomere
studying the DNAchromosomes
protects the chromosomes
of Tetrahymena, a unicellular ciliate organism, she identified a DNA
In the early
sequence thatphase of her research
was repeated several career,
times atElizabeth
the endsBlackburn mapped DNAThe
of the chromosomes. sequences.
function of Whenthis
studying
sequence,the chromosomes
CCCCAA, was unclear. of Tetrahymena,
At the same atime, unicellular ciliatehad
Jack Szostak organism,
made the sheobservation
identified athat DNAa
sequence
linear DNAthat was repeated
molecule, a type of several times at the ends
minichromosome, of the
is rapidly chromosomes.
degraded The function
when introduced intoofyeastthis
sequence,
cells. CCCCAA, was unclear. At the same time, Jack Szostak had made the observation that a
linear DNA molecule, a type of minichromosome, is rapidly degraded when introduced into yeast
cells.
Blackburn presented her results at a conference in 1980. They caught Jack Szostak´s interest and he
and Blackburn decided to perform an experiment that would cross the boundaries between very
Blackburn presented
distant species (Fig 2).herFromresultstheatDNA
a conference in 1980. Blackburn
of Tetrahymena, They caught Jack Szostak´s
isolated the CCCCAA interest and he
sequence.
and Blackburn
Szostak coupleddecidedit to thetominichromosomes
perform an experiment and putthat themwould
backcross
into the
yeastboundaries betweenwhich
cells. The results, very
distant species (Figin2).1982,
were published From the wereDNAstriking
of Tetrahymena, BlackburnDNA
the telomere isolated the CCCCAA
sequence sequence.
protected the
Szostak coupled it from
minichromosomes to thedegradation.
minichromosomes and put
As telomere DNAthem fromback
one into yeast Tetrahymena,
organism, cells. The results, which
protected
were published
chromosomes in anin entirely
1982, different
were striking
one, yeast, the telomere DNAthesequence
this demonstrated existence of protected
a previously the
minichromosomes
unrecognized fundamental from degradation.
mechanism. As telomere
Later on,DNA from one
it became organism,
evident that Tetrahymena,
telomere DNAprotected with its
chromosomessequence
characteristic in an entirely different
is present one,
in most yeast,
plants andthis demonstrated
animals, from amoeba the existence
to man. of a previously
unrecognized fundamental mechanism. Later on, it became evident that telomere DNA with its
characteristic
An enzyme that sequence is present in most plants and animals, from amoeba to man.
builds telomeres
Carol Greider, then a graduate student, and her supervisor Blackburn started to investigate if the
An enzymeofthat
formation builds telomeres
telomere DNA could be due to an unknown enzyme. On Christmas Day, 1984, Greider
Carol Greider,
discovered signsthen a graduateactivity
of enzymatic student,in and herextract.
a cell supervisor Blackburn
Greider started to
and Blackburn namedinvestigate
the enzymeif the
formation
telomerase,of purified
telomereit,DNA andcould
showed be due
thattoit an unknown
consists enzyme.
of RNA On Christmas
as well as proteinDay, (Fig1984,
3). TheGreider
RNA
discovered
component signs turned of enzymatic
out to contain activitythein CCCCAA
a cell extract. Greider
sequence. and Blackburn
It serves named the
as the template whenenzyme the
telomerase,
telomere is purified
built, while it, andthe showed
protein that it consists
component of RNA as
is required forwell
the as protein (Figwork,
construction 3). Thei.e. RNA
the
component turned Telomerase
enzymatic activity. out to contain the CCCCAA
extends telomeresequence. It serves
DNA, providing as the template
a platform that enableswhen DNA the
telomere
polymerases is built,
to copywhile the protein
the entire length of component
the chromosome is required
without formissing
the construction
the very endwork, i.e. the
portion.
enzymatic activity. Telomerase extends telomere DNA, providing a platform that enables DNA
polymerases
Telomeres delay to copy
ageingthe ofentire length of the chromosome without missing the very end portion.
the cell
Scientists now began to investigate what roles the telomere might play in the cell. Szostak´s group
Telomeresyeast
identified delaycells
ageing withof mutations
the cell that led to a gradual shortening of the telomeres. Such cells
Scientists
grew poorly now and began to investigate
eventually stoppedwhat rolesBlackburn
dividing. the telomere might
and her play in the
co-workers cell.mutations
made Szostak´s in group
the
identified
RNA of theyeast cells withand
telomerase mutations
observed that led toeffects
similar a gradual shortening ofInthe
in Tetrahymena. telomeres.
both cases, thisSuchledcells to
grew poorly cellular
premature and eventually
ageing stopped dividing. In
senescence. Blackburn
contrast, andfunctional
her co-workers telomeres made mutations
instead preventin the
RNA of the telomerase
chromosomal damage and anddelayobserved similar
cellular effects in
senescence. Tetrahymena.
Later on, Greider´s In group
both cases,
showed thisthat
ledthe to
premature
senescence of cellular
humanageingcells is alsosenescence. In contrast,Research
delayed by telomerase. functionalin thistelomeres
area has been instead prevent
intense and
chromosomal
it is now known damage
that theand DNA delay cellular
sequence in senescence.
the telomereLater on,proteins
attracts Greider´s thatgroup
formshowed that cap
a protective the
senescence of human
around the fragile endscells is also
of the DNAdelayed
strands.by telomerase. Research in this area has been intense and
it is now known that the DNA sequence in the telomere attracts proteins that form a protective cap
around the fragile ends of the DNA strands.

An important piece in the puzzle human ageing, cancer, and stem cells
These discoveries had a major impact within the scientific community. Many scientists speculated
An important
that telomere piece in the could
shortening puzzlebe human ageing,
the reason for cancer,
ageing, and stemincells
not only the individual cells but also in
These discoveries had a major impact within the scientific community. Many scientists speculated
that telomere shortening could be the reason for ageing, not only in the individual cells but also in

Then and Now: Cancer Treatments from Henrietta Lacks to Today v

the organism as a whole. But the ageing process has turned out to be complex and it is now thought
to depend on several different factors, the telomere being one of them. Research in this area
the organism as a whole. But the ageing process has turned out to be complex and it is now thought
remains intense.
to depend on several different factors, the telomere being one of them. Research in this area
remains intense.
Most normal cells do not divide frequently, therefore their chromosomes are not at risk of
the organism as a whole. But the ageing process has turned out to be complex and it is now thought
shortening and they do not require high telomerase activity. In contrast, cancer cells have the ability
to depend
Most normal on cells
several
do different
not divide factors, the telomere
frequently, thereforebeing
theirone of them. Research
chromosomes are notinatthis
riskarea
of
to divide infinitely and yet preserve their telomeres. How do they escape cellular senescence? One
remains intense.
shortening and they do not require high telomerase activity. In contrast, cancer cells have the ability
explanation became apparent with the finding that cancer cells often have increased telomerase
to divide infinitely and yet preserve their telomeres. How do they escape cellular senescence? One
activity. It was therefore proposed that cancer might be treated by eradicating telomerase. Several
Most normalbecame
explanation cells do not divide
apparent with frequently,
the finding therefore
that cancertheircellschromosomes are not telomerase
often have increased at risk of
studies are underway in this area, including clinical trials evaluating vaccines directed against cells
shortening
activity. and therefore
It was they do not require that
proposed high cancer
telomerase
mightactivity. In contrast,
be treated cancer cells
by eradicating have theSeveral
telomerase. ability
with elevated telomerase activity.
to divideare
studies infinitely
underwayandinyet preserve
this their telomeres.
area, including How evaluating
clinical trials do they escape cellular
vaccines senescence?
directed One
against cells
explanation
with elevatedbecame apparent
telomerase with the finding that cancer cells often have increased telomerase
activity.
Some inherited diseases are now known to be caused by telomerase defects, including certain forms
activity. It was therefore proposed that cancer might be treated by eradicating telomerase. Several
of congenital aplastic anemia, in which insufficient cell divisions in the stem cells of the bone marrow
studiesinherited
Some are underway
diseasesin are
thisnow
area, including
known to beclinical
causedtrials evaluatingdefects,
by telomerase vaccinesincluding
directedcertain
againstforms
cells
lead to severe anemia. Certain inherited diseases of the skin and the lungs are also caused by
with
of elevatedaplastic
congenital telomerase activity.
anemia, in which insufficient cell divisions in the stem cells of the bone marrow
telomerase defects.
lead to severe anemia. Certain inherited diseases of the skin and the lungs are also caused by
Some inherited
telomerase diseases are now known to be caused by telomerase defects, including certain forms
defects.
In conclusion, the discoveries by Blackburn, Greider and Szostak have added a new dimension to our
of congenital aplastic anemia, in which insufficient cell divisions in the stem cells of the bone marrow
understanding of the cell, shed light on disease mechanisms, and stimulated the development of
lead
In to severethe
conclusion, anemia. Certain
discoveries inherited diseases
by Blackburn, of the
Greider and skin have
Szostak and added
the lungs
a newaredimension
also caused by
to our
potential new therapies.
telomerase
understanding defects.
of the cell, shed light on disease mechanisms, and stimulated the development of
potential new therapies.
In conclusion, the discoveries by Blackburn, Greider and Szostak have added a new dimension to our
understanding of the cell, shed light on disease mechanisms, and stimulated the development of
potential new therapies.
Elizabeth H. Blackburn has US and Australian citizenship. She was born in 1948 in Hobart, Tasmania, Australia.
After undergraduate studies at the University of Melbourne, she received her PhD in 1975 from the University
Elizabeth
of H. Blackburn
Cambridge, England, has and US
wasand Australian citizenship.
a postdoctoral researcherShe was University,
at Yale born in 1948 New in Hobart, Tasmania,
Haven, USA. Australia.
She was on the
After undergraduate
faculty at the University studies at the University
of California, Berkeley,ofandMelbourne,
since 1990 she received
has her PhD of
been professor in biology
1975 fromandthe University
physiology at
of Cambridge, England, and was a
the University of California, San Francisco.postdoctoral researcher at Yale University, New Haven, USA. She was on the
faculty
Elizabethat H.
theBlackburn
Universityhas of California, Berkeley,citizenship.
US and Australian and since 1990
She washasborn
beeninprofessor of biology
1948 in Hobart, and physiology
Tasmania, at
Australia.
the
AfterUniversity
Carol W. Greider of California,
undergraduate is studies San
a US citizen Francisco.
at the University
and of Melbourne,
was born in 1961 inshe Sanreceived her PhD in USA.
Diego, California, 1975 She
fromstudied
the University
at the
of Cambridge,
University England, in
of California and was Barbara
Santa a postdoctoral
and in researcher at Yaleshe
Berkeley, where University,
obtainedNew Haven,
her PhD USA. She
in 1987 withwas on the
Blackburn
Carol
as her W.
faculty Greider
at the
supervisor. is a US
University
After citizen andresearch
of California,
postdoctoral was born
Berkeley, and
at insince
Cold 1961 in Harbor
1990
Spring San
has Diego,
been California,
professor
Laboratory, USA.
of biology
she She
andstudied
was appointed at the
physiology at
professor
University
thethe
in of California
University of in
of California,
department Santa Barbara
biologyand
San Francisco.
molecular andin Berkeley,
genetics at where
JohnssheHopkins
obtained her PhD School
University in 1987 of
with Blackburn
Medicine in
as her supervisor.
Baltimore in 1997. After postdoctoral research at Cold Spring Harbor Laboratory, she was appointed professor
in theW.
Carol department
Greider isofa molecular
US citizen biology
and wasandborngenetics
in 1961at inJohns HopkinsCalifornia,
San Diego, UniversityUSA.
School
She of Medicine
studied in
at the
Baltimore
University in
of1997.
Jack W. Szostak California in SantaHe
is a US citizen. Barbara andinin1952
was born Berkeley, whereUKshe
in London, andobtained
grew upher PhD in 1987
in Canada. with Blackburn
He studied at McGill
as her supervisor.
University Afterand
in Montreal postdoctoral research atinCold
at Cornell University Spring
Ithaca, NewHarbor Laboratory,
York, where she was
he received his appointed professor
PhD in 1977. He has
Jack
in the
been W. Szostak
HarvardisMedical
atdepartment a US
of citizen.
molecular
SchoolHesince
was born
biology inand
and
1979 1952is in
genetics London, UK and
at Johns
currently grew
Hopkins
professor up in Canada.
University
of genetics He studied
School atGeneral
McGill
of Medicine
at Massachusetts in
University
Baltimore
Hospital in
inin Montreal
1997.
Boston. He isand ataffiliated
also Cornell University in Ithaca,
with the Howard New York,
Hughes where
Medical he received his PhD in 1977. He has
Institute.
been at Harvard Medical School since 1979 and is currently professor of genetics at Massachusetts General
Hospital in Boston.
Jack W. Szostak is aHeUSiscitizen.
also affiliated
He was with
bornthe Howard
in 1952 Hughes UK
in London, Medical Institute.
and grew up in Canada. He studied at McGill
University in Montreal and at Cornell University in Ithaca, New York, where he received his PhD in 1977. He has
been at Harvard Medical School since 1979 and is currently professor of genetics at Massachusetts General
References:
Hospital in Blackburn
Szostak JW, Boston. He EH.isCloning
also affiliated with theonHoward
yeast telomeres Hughes
linear plasmid Medical
vectors. CellInstitute.
1982; 29:245-255.
References:
Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell
Szostak JW, Blackburn EH. Cloning yeast telomeres on linear plasmid vectors. Cell 1982; 29:245-255.
1985; 43:405-13.
Greider CW, Blackburn EH. Identification of a specific
A telomeric sequence telomere
in the RNA of terminal transferase
Tetrahymena activity
telomerase in Tetrahymena
required extracts.
for telomere repeatCell
1985; 43:405-13.
synthesis. Nature 1989; 337:331-7.
References:
Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat
Szostak JW, Blackburn EH. Cloning yeast telomeres on linear plasmid vectors. Cell 1982; 29:245-255.
synthesis. Nature 1989; 337:331-7.
Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell
1985; 43:405-13.
The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel
Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat
Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important
synthesis. Assembly,
discoveries Nature
The Nobel for
1989;
the benefit of337:331-7.
mankind.
consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel
Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important
discoveries for the benefit of mankind.
Nobel Prize® is the registered trademark of the Nobel Foundation
The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel
Committee
Nobel Prize®evaluates the nominations.
is the registered trademarkSince
of the1901
Nobelthe Nobel Prize has been awarded to scientists who have made the most important
Foundation
discoveries for the benefit of mankind.

Nobel Prize® is the registered trademark of the Nobel Foundation

Then and Now: Cancer Treatments from Henrietta Lacks to Today vi