"In some respects, micronuclei are similar to primary nuclei," Pellman remarks, "but much about their function and composition is unknown. Previous studies differ on whether micronuclei replicate or repair their chromosomes as normal nuclei do. The ultimate fate of these chromosomes is unclear as well: Are they passed on to daughter cells during cell division or are they somehow eliminated as division proceeds?"
One clue that odd-man-out chromosomes themselves may be subject to damage -- and therefore be involved in cancer -- emerged from Pellman's previous research into aneuploidy. "We found that cancer cells generated from cells with micronuclei also have a great deal of chromosome breakage," Pellman explains. But researchers didn't know if this was a sign of connection or of coincidence.
Another clue came from a recently discovered phenomenon called "chromothripsis," in which one chromosome of a cancer cell shows massive amounts of breakage and rearrangement, while the remainder of the genome is largely intact. "That finding leapt off the page of these studies -- that such extensive damage could be limited to a single chromosome or single arm of a chromosome," Pellman says. "We wondered if the physical isolation of chromosomes in micronuclei could explain this kind of highly localized chromosome damage."
To find out, Karen Crasta, PhD, of Pellman's lab and the study's lead author, used a confocal microscope to observe dividing cells with micronuclei. She found that while micronuclei do form duplicate copies of their chromosomes, the process is bungled in two respects. First, it is inefficient: part of the chromosome is replicated and par
|Contact: Bill Schaller|
Dana-Farber Cancer Institute