The cell must establish and then maintain centromeric heterochromatin to ensure that each chromosome pair is stable and securely linked together until its time to separate, said Janet Partridge, Ph.D., assistant member of the St. Jude Department of Biochemistry. Otherwise, the chromosome pairs would drift apart and leave daughter cells with too many or too few chromosomes. Partridge is the reports senior author.
The St. Jude team studied combinations of molecules in yeast called the RITS and RDRC complexes, which together with an enzyme called Clr4 (Suv39 in humans), establish and maintain centromeric heterochromatin in the yeast cell during a carefully choreographed series of steps.
RITS is composed of the proteins Ago1, Tas3 and Chp1 and works closely with RDRC. RDRC produces a type of genetic material called double-stranded RNA, which an enzyme, called dicer, then chops into smaller pieces called small interfering RNA (siRNA). siRNA is bound by RITS, and in turn, helps RITS to reinforce the centromeric heterochromatin and keep it stable.
In addition, the Clr4 enzyme puts chemical tags onto the histone spool in a process called methylation. Methylation attracts a protein called Swi6 (HP1 in humans) to the chromosome to reinforce heterochromatin.
Previously, scientistsincluding Partridges teamshowed that cells lacking any component of RITS, RDRC or the Clr4 complex fail to assemble intact centromeric heterochromatin and suffer loss of chromosomes. However, researchers did not know whether the same components of these complexes are needed to support both establishment and the maintenance of centromeric heterochromatin. Therefore, Partridges team developed specially modified yeast cells that allowed them to study
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Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
14-Jun-2007