44284BFBd01 - The hallmarks of cancer Telomeres Limitless...

Info iconThis preview shows pages 1–12. Sign up to view the full content.

View Full Document Right Arrow Icon
The hallmarks of cancer Telomeres
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Limitless Limitless Replicative Replicative Potential Potential
Background image of page 2
Telomeres at the end of all eukaryotic chromosomes
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Cellular Lifespan (I) • The machinery determining the replicative potential has been associated with telomeres – During successive cellular divisions the telomeres in normal human cells shorten progressively – Telomeres are shorter in most somatic tissues from older individuals compared to younger individuals – Telomeres are shorter in somatic cells than in germ line cells
Background image of page 4
Telomere length in normal human tissues
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Cellular Lifespan (I) • The machinery determining the replicative potential has been associated with telomeres – Childeren born with progeria (early aging syndrome) have shorter telomeres in some tissues compared to age-matched controls – Telomeres progressively shorten when cells are grown in culture – Telomeres function as a ‘molecular clock’ (mitotic counter) – Once telomeres erode down below a threshold length, the senescence phenotype is provoked (not well understood) • Normal human cells grown in vitro replicate for a limited period of time before entering ‘ SENESCENCE’ (Mortality stage 1 = M1 or Hayflick limit) – Irreversible permanent growth arrest but cells remain viable
Background image of page 6
Function of telomeres • Telomeres are tandem repeats (TTAGGG/CCCTAA) n – Length varies between species and chromosomes • Human telomeres 10-15 kb • Mouse telomeres – Mus Musculus (>30kb); Mus Spretus (9-13 kb) • Telomeres end with a short single stranded 3’ overhang – this overhang is the substrate for telomerase • Telomeres are crucial for the life of a cell – Prevent the ends of linear chromosomes from appearing as DNA breaks – They protect chromosome ends from degradation and fusion – They allow complete chromosome replication and they position the chromosomes within the nucleus
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Replication of linear chromosomes presents a special problem - End replication problem •DNA polymerase can only synthesize a new strand of DNA as it moves along the template strand in the 3’ 5’ direction •DNA replication in linear chromosomes is different for each of the two strands •The lagging strand is synthesized as discontinous Okazaki fragments •Even if the replication starts at the very end of the lagging strand of DNA some bases will not be replicated since the terminal RNA primer can not be replaced by DNA Labile RNA primer
Background image of page 8
Replication of linear chromosomes presents a special problem - End replication problem •Human telomeres lose ~ 100 base pairs from their telomeric DNA at each mitosis •This represents about ~16 TTAGGG repeats at this rate after ~125 mitotic divisions the telomeres would be completely gone
Background image of page 9

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
The telomere hypothesis of cellular aging and immortalization - Mortal Cells Mean Telomere length
Background image of page 10
Cellular Lifespan (II) • Cancer cells proliferate idefinitely and are therefore considered to be immortal – Cancer cells have telomeres with a stable length
Background image of page 11

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 12
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 05/28/2010 for the course WE MOBI000000 taught by Professor Geertberx during the Spring '10 term at Ghent University.

Page1 / 46

44284BFBd01 - The hallmarks of cancer Telomeres Limitless...

This preview shows document pages 1 - 12. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online