Secrets of the cell
Findings may shed light on new directions for
at the U.Va. Health System
have gotten closer to understanding what makes cells grow and
divide with two key discoveries about enzymes that alter histones.
These findings, which may present new treatment targets for some
cancers, are published in early August issues of Cell and Nature.
"DNA is the mission control of our cells, but how our genetic
template knows what to do, how to replicate and divide faithfully
to each daughter cell, has been a long-standing mystery. With
these and other recent discoveries, we have begun to identify
controllers for specific parts of the cell cycle," said C.
David Allis, the Byrd Professor of Biochemistry
at U.Va., who heads one of the research labs responsible for the
Cell and Nature studies. "These findings put us closer to
complete understanding of the cell cycle which will ultimately
have enormous consequences for therapy and drug design, particularly
The cell cycle is an ordered set of events, culminating in cell
growth and division into two daughter cells. The nucleus of each
cell contains genetic information in the form of chromatin, a
highly folded ribbon-like complex of deoxyribonucleic acid (DNA)
wrapped around a class of proteins called histones. Histones,
and specifically processes that modify histones, are thought to
play a large role in the complex processes of gene expression
and cell division, a process that underlies tissue growth and
"Because cancer is a disease in which regulation of the cell
cycle goes awry, a better understanding of these processes should
lead to new cancer treatments," Allis explained.
Cell paper, which includes the work of M. Mitchell Smith, professor
of microbiology at U.Va., and Rueyling Lin, assistant professor
of molecular biology at the University of Texas Southwestern Medical
Center at Dallas, describes the discovery of enzymes that play
an important role in cell division by altering histones through
a reversible modification process called phosphorylation. One
of these enzymes, known as aurora, is found in excess in human
tumors, leading the researchers to believe that aurora can be
considered a treatment target for certain cancers.
The finding reinforces the emerging theme that modifications to
histones, and changes in chromatin in general, are key to the
normal management of the cell cycle.
study published in Nature relays the discovery of what Allis calls
an additional layer of regulation or an "on/off switch"
for a second process that alters histones, a key finding done
in collaboration with another team led by Thomas Jenuwein of the
Research Institute of Molecular Pathology in Vienna, Austria.
Called histone methylation, it is thought to be another step in
the cell division process that may regulate the phosphorylation
discussed in the Cell paper.
these studies underscore that the normal regulation of certain
enzymes are vital to cell division and replication and that inappropriate
regulation of their activities is closely associated with the
formation of cancer," Allis said. "The implications
of this research, while basic, are far reaching for human biology