Surprising tail for worm telomeres

Source: Salk Institute

A team of scientists at the Salk Institute for Biological Studies has discovered that the roundworm C. elegans constructs the protective tips of its chromosomes - known as telomeres - with a little more panache than do mammals, a finding that could deepen our understanding of the interrelationship of ageing and cancer.

In a study reported in March 7 issue of the journal Cell, researchers in the laboratory of Associate Professor Jan Karlseder showed that unlike mammals, who normally terminate both ends of every chromosome with a string of DNA rich in the base guanine (G), C. elegans can also decorate a telomere with a different motif, a strand abundant in the base cytosine (C).

Karlseder said discovering this deviation from the standard G-tail issued to mammals was completely unanticipated.

"Telomeres protect the ends of chromosomes like a glove," he said. "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."

Safeguarding the ends of linear chromosomes is essential for any animal's survival.

"Telomere loss can lead to chromosome fusion. If that happens when a cell divides its chromosomes could randomly break, leading to a condition known as genome instability, a major cause of cancer."

Telomeres are the object of intense investigation because these structures represent the physical link between cancer and aging research. Normally, telomeres shorten as cells divide, acting as a kind of cellular clock ticking down a cell's age: when they shorten to a critical point the cell dies.

However, in cancer, the clock runs backwards and telomeres aberrantly elongate, turning what could be a cellular fountain of youth into a potential malignancy.

Karlseder and lead author Dr Marcela Raices discovered the unique C-tails in collaboration with Associate Professor Andrew Dillin.

The team first found that not only did worm telomere tails come in two flavours but that each was uniquely attached to the chromosome. Double-stranded DNA terminates with mirror-image ends, like right and left hands. In mammals, G-tails extend from the "right hand"- or 5' end. But worm C-tails hung off the DNA "left hand" or 3' end.

They then identified two novel worm proteins that bound preferentially to either C- or G-tails. They capped the study by showing that worms lacking either protein exhibited abnormal telomeres, suggesting that each protein - like a somewhat similar protein found in mammalian cells - is part of the machinery regulating the length of C- or G-tailed telomeres.

An obvious question now emerging from the study is whether C-tails are unique to worms or whether they have been overlooked in mammals.

"It is premature to think that C-tails do not exist in human cells," Karlseder said. "We may find them in mammalian cells under certain circumstances, and if so, they could play a role in telomere maintenance and in cancer."