AMHERST, Mass. - A University of Massachusetts microbiologist is one of a group of six researchers offering a major step forward in developing a model explaining DNA repair, recombination, and replication, in a report appearing in today''s issue of the journal Nature. The study, "Re-establishment of Inactivated Replication Forks as a Bacterial Housekeeping Function," gives new insight into the sequence of events involved in cell division, information that will be of great help to molecular biologists involved in cancer and other medical research, according to Steven J. Sandler, professor of microbiology.
For many years, the functions of DNA recombination, repair, replication, chromosome segregation, and cell division were thought to be related or coordinated in the cell, but no one really knew how, according to Sandler. The Nature article summarizes some seemingly unrelated pieces of data, and proposes that these different processes are actually related and delicately coordinated. Moreover, the coordination revolves around the ability of the cell to fix replication forks points at which DNA replication takes place that have been derailed by ordinary, day-to-day DNA damage.
According to Sandler, "This gives a new spin on data so that it now is illuminating instead of confusing. We have interpreted old studies and combined that information with our own research, to see recombination in a new light. There is a link between DNA replication and recombination that we never knew before."
Using E. coli as a model, the researchers looked at mutations in this simple organism with a single chromosome to see how these mutations affected the ability to restart replication. They knew that special sets of proteins called primosome assembly proteins were important in this process, especially one called priA. When priA is present in the cell, nucleoids or that part of the cell of a simple organism that roughly corresponds to a nucleus in a more complex one separate, and cells divide properly. Without priA, nucleoids fail to separate properly, and the replication process is stalled.
"Anytime there is replication, forks can get damaged," explained Sandler. "What''s new in this study is that we see now that everything that happens in a cell does so almost simultaneously, so that all the key ingredients must be present for the scheme to work properly. We now know that, when DNA is repaired, the cell uses priA to complete a kind of housekeeping function so it can restart the replication process at the forks.
"It s as if the cell must be sure that all this has happened correctly before it segregates the chromosomes and divides," said Sandler.
Sandler is conducting research into the role of primosome assembly proteins in E. coli with help from a grant from the American Cancer Society. Other scientists contributing to the article were Myron F. Goodman of the University of Southern California, Michael M. Cox of the University of Wisconsin, Kenneth N. Kreuzer of Duke University Medical Center, David J. Sherratt of Oxford University, and Kenneth J. Marians of Memorial-Sloan Kettering Cancer Center, New York.
Steven J. Sandler is available for interviews at 413/577-4391.