Wednesday, March 12, 2008

‘C’ the overhang: Chromosomal telomeres in roundworms C. elegans

Posted by Adam O'Donoghue, Student No # 41719350

An interesting study was performed at the Salk Institute for Biological Studies by Associate Professor Jan Karlseder on the chromosomal structure of the roundworm C. elegans. The study examined telomere formation at the ends of chromosomes, and their possible role in the formation of cancer cells. Most animals protect their chromosomes with terminal DNA sequence overhangs rich in the base guanine (G). The roundworms, however, were found to be able to form another protective overhang, one rich in the base cytosine (C).

Karlseder, in an article published by “Science Daily”, commented on his team’s findings, saying that they were very unexpected. “Telomeres protect the ends of chromosomes like a glove” he stated. “In mammals, telomeres have a single stranded overhang with a ‘TTAGGG’ sequence about 150 bases long. We found that in worms there can also be a single-stranded overhang of a C-containing strand”.

The formation of telomeres on chromosomes is an essential part in DNA replication and mitosis, and is necessary in all animal cells. Telomeres deteriorate with age and are associated with cellular senescence, abnormal growth and death. Karlseder explains: “Telomere loss can lead to chromosome fusion, if that happens when a cell divides, its chromosomes could randomly join and break, leading to a condition know as ‘genome instability’, a major cause of cancer”.

The study found that the G- and C-tails uniquely connected to a particular side of the DNA molecule. G-tails extended from the 5’ end, and C-tails from the 3’ end. It was also discovered that two unique proteins in the worm bound preferentially to the C or G overhangs, thus affecting the length of the telomeres and possibly influencing the cells bio-clock.

The significance and scope of the findings remain to be determined by comparable studies on other animal species. Karlseder noted that “C. elegans is an established model to studying age, We can screen the whole worm genome relatively cheaply in a few months. The same experiment in human cells would take years and probably ten times the money. We want to exploit the C. elegans system and then translate our findings into a human system.”

However, more research is needed to actually determine whether the C-tails are unique to worms or have just been overlooked within mammals. “It’s premature to think that C-tails do not exist in human cells. We may find them in mammalian cells under certain circumstances, and if so, they could play a role in telomere maintenance and in cancer.”

The study has potential applications in many different areas of research, including the development of possible cancer therapies involving differentially blocking telomere synthesis in cancer cells to curtail cell division. Such applications remain speculative until more detailed studies are conducted to determine the molecular processes involved in telomere formation and function.

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