Scientists are discovering the proteins that control the way human DNA
copies itself, a breakthrough that may lead to new treatments for cancer
or heart disease.
Dr. R. Sanders Williams, professor of internal medicine and chief of
cardiology at UT Southwestern Medical Center at Dallas, has identified
a protein thought to function in the initiation of DNA replication. The
discovery was made during his year-long sabbatical at Cold Spring Harbor
Laboratory in New York where he conducted research with Dr. Bruce Stillman.
The discovery of the gene, termed p62cdcd6, is reported in the January
7th issue of The Proceedings of the Academy of Sciences.
"When cells divide, each of the three billion nucleotides in the
entire human genome must be copied once, and only once, and this process
must be completed in just a few hours," Williams said. "If the
process goes awry by producing too many or too few copies of a segment
of the genome, serious problems can result."
Williams said Stillman has been a major leader in the field of cell-cycle
control, using yeast models to learn how DNA replication is triggered.
"A yeast protein called cdc6p proves to be a critical regulatory
component that is involved in both replication licensing--preparing the
chromosome to be ready to replicate--and in the process by which the cell
replicates DNA precisely once in each cell cycle," Williams said.
Compared to yeasts, very little is known about what triggers DNA replication
in higher organisms, including humans. The discovery of so-called "initiator"
proteins like p62cdcd6 in human cells opens the door to greater understanding
of mechanisms of tumor development and the events by which certain cells,
like those of the heart, lose the capacity to replicate DNA.
Authors Williams, Stillman, and Dr. Ralph Shohet, assistant professor
of internal medicine at UT Southwestern, speculate that the human DNA-replicator
protein will serve a similar function as the yeast DNA-replicator counterpart.
"It appears the basic machinery of DNA replication and origin firing
is conserved across all of life," Williams said.
Role of Protein in Human Cancers Still to Be Elucidated
The discovery is pertinent to cancer because mutations in yeast cdc6p
cause abnormalities very similar to human malignancies. Scientists are
not yet sure of the role of p62cdcd6 in human tumors, but it could become
a novel target for therapies to stop cells from replicating DNA.
Knowledge about this protein also may be useful in heart disease.
"There are some cells that don't replicate their DNA when we want
them to--like heart cells after a heart attack," said Williams, who
is director of the Frank M. Rybum Jr. Cardiac Center at UT Southwestern
and holder of the James T. Willerson, MD, Distinguished Chair in Cardiovascular
The work was communicated to the journal by Dr. James D. Watson of Cold
Spring Harbor Laboratory and was supported by funds from the National Institutes