Like the plastic aglets at the ends of shoelaces, telomeres normally protect the ends of chromosomes from instability and degradation – the hallmarks of cancer. Johns Hopkins University researchers recently revamped the model of how degradation happens. Previously, end-to-end chromosomal fusion events and breakage were regarded as the prime initiator, but new work reveals that exonucleases first chew away at chromosomes with short telomeres. Carol Greider, a Johns Hopkins professor, calls the result "a surprise."
Greider and graduate student Jennifer Hackett began work after observing in Saccharomyces cerevisiae that chromosomal rearrangements in the absence of telomerase consisted entirely of translocations near chromosome ends. To discover what initiates this, they followed the loss of genetic markers along the chromosome.1 "We found a progressive loss from the end toward the centromere," says Greider. Marker loss was found to be dependent on the exonuclease Exo1p, indicating that enzymatic degradation was the initiating mechanism, ...
