The study was published in the October 20, 2006 issue of the journal Molecular Cell
“These results are exciting because they reveal for the first time how these proteins can dynamically assemble and change their shape to join DNA ends during DNA replication and repair,” said a senior author of the paper John Tainer, who is a professor at Scripps Research, member of Scripps Research’s Skaggs Institute for Chemical Biology, and co-principal investigator of the Structural Cell Biology of DNA Repair project in Berkeley Lab’s Life Sciences Division.
As the genetic material, DNA is surprisingly reactive and under continuous assault from environmental toxins and reactive cellular metabolites, so a means of repairing DNA damage is essential to maintaining the integrity of our genetic blueprint for future generations.
DNA ligases are enzymes that are an essential part of this process, repairing millions of DNA breaks generated during the normal course of a cell’s lifetime. Because the reaction joining the ends of DNA strands to restore the double helix is catalyzed by ligase enzymes and because this reaction is essential and abundant in dividing cells, DNA ligases are attractive targets in the development of new treatments for cancer and other diseases.
Ligase does its job in concert with another ring-shaped protein known as a sliding clamp. Sliding clamps like the human PCNA protein are master regulators of DNA repair, providing docking sites that recruit repair enzymes to the site of damage.