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I'm Dr. Jess Buxton,I'm a geneticist at University College London.This talk is on the role of "Telomeres and Cardiovascular Disease".
I'll start with an outline of what telomeres are,and the role of the enzyme telomerase in telomere function beforecovering telomeres and their role in monogenic disease and their role innormal aging and then the rest of the talk will focus on the role of telomeres and inparticular telomere length and its role in risk of cardiovascular disease.
So, what are telomeres? Well,they're the protective caps found at the ends of all linear chromosomes,in this picture here they've been stained with a fluorescent dye.
So, telomeres are composed of repetitive sequences of DNA,these are all G rich but are different in different species.In jellyfish it's TTAGGG and thatalso happens to be the same as all vertebrates including humans,but it's not just one copy of this repeat unit it'smany thousands and it's there to act as a buffer to protect the coding sequences.Every time a cell divides,it will lose a little bit of the DNA from the ends ofall its chromosomes because of the way DNA is replicated.The cell's DNA replication machinery can'tquite copy to the end of one half of the double helix strand,so a little bit is lost,this is known as the end replication problem.So, to prevent this eroding the coding sequences,the genes and regulatory sequences,the telomeric DNA is there and acts as a buffer sothat is lost rather than the coding sequences in the rest of the chromosome.
So, in vertebrates including humans,telomeres are composed of many units of the six base pair repeatTTAGGG bound to a complex of proteins known collectively a shelterin,six core proteins and several additional proteins,as you can see in this diagram.Shelterin serves to protect the telomeric DNA and prevent the cellsDNA repair mechanisms from recognizingthe ends of linear chromosomes as double-stranded DNA breaks.So, they prevent chromosome fusion.So, in addition to their buffering function whereby every timea cell divides a little bit of the telomeric DNA is lost,with the addition of the shelterin complex it's also preventing fusion,so they're preventing both degradation and fusion.So, telomeres are absolutely crucial for genomic integrity of the cell.So, as I've mentioned in most cells,every time the cell divides in most tissues,the telomeres we'll get a little bit shorter every time.This isn't the case in some cell types particularly germ cells and stem cells,where an enzyme called telomerase is able to replacetelomeric DNA repeats and it does this using its own RNA template.It's unusual enzyme that it's composed ofboth an RNA molecule known as TERT which provides a template toadd on additional telomeric DNA repeat unitsand the TERT protein which is a reverse transcriptase.It's active in germ cells and stem cells to maintain the telomeres in those cell types.Telomerase is also reactivated in around 90 percent of cancer cells and this is howcancer cells become immortal and don'tdie out and become senescent as other cell types do.