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Protein involved in DNA replication, centrosome regulation linked to dwarfism, small brain size
Date:7/31/2012

Cold Spring Harbor, NY Research published Aug. 1 by scientists at Cold Spring Harbor Laboratory (CSHL) links gene mutations found in some patients with Meier-Gorlin syndrome (MGS) with specific cellular dysfunctions that are thought to give rise to a particularly extreme version of dwarfism, small brain size, and other manifestations of abnormal growth which generally characterize that rare condition.

Although only 53 cases of Meier-Gorlin syndrome have been reported in the medical literature since the first patient was described in 1959, it is a malady whose mechanisms are bringing to light new functions for some of the cellular processes common to all life. Pathology related to MGS is traced in the new research to one of these, the fundamental process called mitosis in which cells replicate their genetic material and prepare to divide into two identical "daughter" cells.

CSHL President and Professor Bruce Stillman, Ph.D., a cancer biologist who has made seminal discoveries over three decades that have helped reveal the exquisite choreography of how chromosomes are duplicated in cells, led the new research, which suggests how, during mitosis, mutant versions of a protein called Orc1 contribute in two distinct ways to severe MGS pathology. The research is published online ahead of print in Genes & Development.

Components of the cellular replication machinery

Orc1 is the largest of six proteins that form parts of a cellular machine called the origin recognition complex, or ORC. As Stillman and others discovered 20 years ago, ORC in human cells attaches to DNA at specific locations throughout the genome when a cell is preparing to duplicate its genetic information and go through cell division. These locations are called replication start sites or origins. When ORC and several other helper proteins attach at these positions, each of the assembled groups of proteins is said to form a pre-replication complex (
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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