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Add, subtract, divide equals life

Apr 11, 2012

Blog posting from UCSD based on a Ludwig study published in Nature

April 8, 2012, San Diego—Centromeres are regions of DNA and proteins on each chromosome that both link together sister chromatids and ensure accurate chromosome segregation and distribution during cell division or mitosis. When centromeres don’t work right, the result can be catastrophic. Indeed, aberrant division and chromosomal instability are hallmarks of cancer cells, especially the most aggressive types.

Yet despite their existential importance – “Chromosome segregation is the key event of cell division and fundamental to understanding life,” said Arshad Desai, PhD, investigator at the Ludwig Institute for Cancer Research and professor of Cellular and Molecular Medicine at UC San Diego – centromeres remain imperfectly understood more than a century after German biologist Walther Flemming first described them.

In a letter published on April 8th in the advance online edition of the journal Nature,  Desai and colleagues fill in some critical details, describing the germline transcription process that defines centromeres in Caenorhabditis elegans, a nematode whose similar molecular mechanisms make it a model for human biology.

“How does a chromosomal region know it is a centromere and how is that information maintained. That’s the topic of our paper,” said Desai.

The work goes beyond simply advancing basic scientific understanding. Current cancer drugs like taxol and vinca alkaloids work by perturbing cell division. The problem is that these drugs can be toxic in non-dividing cells, such as neurons. A better understanding of how centromeres form and function could lead to more finely tuned or different ways for perturbing cell division.

Perhaps more significantly, said Desai, understanding centromeres will help in designing artificial chromosomes. “We currently rely on viruses for stable delivery of genetic information,” Desai said. “But this has the disadvantage that viruses integrate at random into genomes, which can negatively impact the patient.”

An artificial chromosome, with all of the genetic information tucked into the appropriate places, would preclude the need for viral vectors. And, said Desai, “the major limitation to designing true artificial chromosomes is our lack of understanding of centromeres.”

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