Telomeres the ends of chromosomes act like caps on shoe laces. They prevent the chromosomes and the genes there in, from becoming untied there by degenerating the DNA. They also serve another function. DNA has repair mechanism that continuously checks for signals that indicate damaged parts of DNA. If there are minor damages, this mechanism, repairs the DNA while stopping the cell division until this repairing is complete. (of course, if the damage is extensive, the cell goes into programmed death or Apoptosis).
In the latest issue of the journal Nature, Miguel Godinho Ferreira, Principal Investigator at the Instituto Gulbenkian de Ciência (IGC) in Portugal, lead a team of researchers to shed light on a paradox that has puzzled biologists since the discovery of telomeres, the protective tips of chromosomes: while broken chromosome ends generated by DNA damage (such as radiation or cigarette smoke) are quickly joined together, telomeres are never tied to each other, thus allowing for the correct segregation of the genetic material into all cells in our body.
Complete loss of telomeres results in sticky chromosome-ends that join to each other creating to genetic chaos – the very initial steps of cancer.
Understanding how the tips of the chromosomes are protected from DNA repair and how the cells respond when they are unprotected will provide insights into the initial stages of tumourgenesis, ageing and future therapeutic interventions.
Cells respond to broken or damaged DNA by arresting their cell cycle while the damage is repaired. If the tips of chromosomes were recognized as broken DNA, cells would be constantly trying to mend the ends of chromosomes, leading to cell death and mutations in the DNA. Telomeres – the caps made up of protein and DNA at the tips of chromosomes – stop this from happening.
Through a series of meticulous experiments the Portuguese team, in collaboration with researchers at University of Illinois, Chicago, reveal that the crux lies in the changes of a protein, a Histone modification, located close to the telomeres. Histones are found along the entire length of all chromosomes, helping to package the DNA and also playing a role in regulating gene activity. Using fission yeast (used to make bread and beer) as a model organism, the researchers found that one of the Histones neighbouring the telomeres lacks a chemical signal, thus rendering the DNA damage recognition machinery incapable of arresting the cell cycle.