Discovery helps explain how cells package DNA


COLUMBUS, Ohio Researchers have discovered a protein that helps cells package long strands of DNA into a tight ball that fits into the nucleus during cell division.

The study, done in yeast, should help researchers better understand how human cells cram more than 7 feet of DNA--the total length of the genetic material in our 46 chromosomes--into the nucleus, the tiny capsule that holds the chromosomes inside the cell.

The study was published in the April 23 issue of the journal Molecular Cell.

The protein, known as Hif1p, works in conjunction with an enzyme complex to add histone proteins to newly made DNA. Histones are proteins that form tiny spools around which DNA is wound during packaging. The combination of DNA and its proteins is known as chromatin.

"DNA is the brains behind all that happens in a cell," says lead investigator Dr. Mark R. Parthun, assistant professor of molecular and cellular biochemistry and a researcher with The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

"So the packaging of DNA into chromatin is very important for controlling what goes on in the cell."

For example, certain stretches of DNA must be reachable at certain times to control cell division and to turn genes on or off.

"If the DNA isn't properly packaged, that's not going to work right," he says.

The proper packaging of DNA is important for cancer cells, too. Cancer is caused by unrestricted cell division. Parthun's research might therefore help lead to drugs that can block this process and lead to new cancer therapies.

The biochemical pathways that cells use to package DNA in the nucleus remain poorly understood. In 1996, Parthun discovered an enzyme complex in yeast that cells use to assemble histones. He found that the enzyme, known as a type-B histone acetyltransferase (composed of the proteins Hat1p and Hat2p), modifies the histone proteins by adding chemical units known as acetyl groups.

The present study shows that the Hat B enzymes not only chemically modify histone proteins in cytoplasm--the region of the cell outside the nucleus--but that they remain attached to the histones as the proteins travel into the nucleus.

There, Parthun and his colleague, Xi Ai, a graduate student in The Ohio State University biochemistry program, found that the molecular threesome is joined by a fourth member, the newly discovered protein, Hif1p.

Last, the complex is joined by a fifth and still-unidentified protein that helps with that final step: adding the histone to DNA to form chromatin.

Next, Parthun wants to learn why histones must be modified by the addition of acetyl groups during chromatin assembly. He also wants to understand the role of the Hif1 protein in the process and identify the unknown protein that's needed for the final step of chromatin assembly.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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