Scientists have discovered a DNA sequence that is involved in controlling the timing of DNA replication. Because alterations in DNA replication timing are associated with cancer, this discovery may lead to improved methods for cancer detection. The research was published in the Journal of Biological Chemistry.

Before a cell can divide, it must duplicate its DNA. Duplication, which occurs during the S phase of the cell cycle, is initiated at many replication origins in the DNA molecule. These replication origins fire at specific times throughout S phase, causing each segment of the genome to replicate at a precise time.

"S phase lasts about 8 hours in human cells and about 40 minutes in cells of the fission yeast, Schizosaccharomyces pombe," explained Joel A. Huberman of Roswell Park Cancer Institute. "In both cases, some portions of DNA molecules are nearly always duplicated early in S phase while other portions are nearly always duplicated late."

Until recently, very little was known about how cells control replication timing. Studies in budding yeast (Saccharomyces cerevisiae) have suggested that, by default, replication origins fire early in S phase, but they can be forced to fire later by flanking and internal DNA sequences. Now, Huberman and Chulee Yompakdee have discovered a stretch of DNA that verifies this hypothesis.

"Interestingly," noted Huberman, "in many cancer cells, the normal order of DNA replication is altered: regions that should replicate late sometimes replicate early and vice versa." As a result, tests for DNA replication timing may eventually become a method for the early detection of cancer.

"Replication timing assays are one of many promising techniques that are currently being studied that may, in the future, allow much earlier cancer detection than is possible today," concluded Huberman.

SOURCES:
Journal of Biochemistry and Molecular Biology, October 1, 2004
American Society for Biochemistry and Molecular Biology (http://www.asbmb.org)