Faculty Member Scott Keeney

Research by Memorial Sloan-Kettering Cancer Center investigators has revealed the first step of how cells repair a certain type of DNA damage. If not properly repaired, DNA damage can lead to cancer or cell death.

Molecular biologist Scott N. Keeney had previously shown that a protein called Spo11 cleaves DNA during meiosis -- the process of cell division that creates eggs and sperm -- and attaches itself to the broken ends. The same type of DNA breaks occur in cells treated with a class of chemotherapy drugs called topoisomerase II inhibitors. Removing the Spo11 protein from the ends of broken strands is the first crucial step in repairing those breaks.

In their latest work, published in the August 18 issue of Nature, Dr. Keeney's laboratory found that Spo11 is removed with an enzyme called the Mre11 complex. (For a related story about Mre11, see page 5.) Mutations in Mre11 already were associated with an inability to repair DNA damage. [PubMed Abstract]

Much of this work was done in the yeast S. cerevisiae, which is an important model system for studying cell function, but the team also showed that the process occurs the same way in mice.

"We're excited by these findings because they provide our first glimpse of the workings of a previously unknown DNA repair pathway," Dr. Keeney said. "We're currently testing whether the same repair mechanism applies when topoisomerase II is inhibited."

---