Scripps scientists uncover mimicry at the molecular level that protects genome integrity
The new study, which was published on April 12, 2009, in an advanced online edition of the journal Nature Structural & Molecular Biology, draws new parallels between the Rad60 DNA repair factor and SUMO, a small ubiquitin-like modifier, which are both essential for maintaining genome stability during replication.
"This collaborative study between our laboratory and the Scripps Research Tainer group shows the very first indication of mimicry in the SUMO pathway," said Scripps Research Assistant Professor Michael "Nick" Boddy, Ph.D., who was senior author of the study. "By mimicking a particular surface feature of SUMO, Rad60 competes for binding to an essential enzyme of the SUMO machinery. Thus, Rad60 is a previously undefined member of the SUMO team."
Maintaining genome stability is critical to an organism’s survival because genetic defects can promote tumors, aging, and neurodegenerative disease. The genome is particularly vulnerable to spontaneous and damage induced alterations during the replication or S phase of cell division. To ensure the high-fidelity completion of replication, cells engage critical mechanisms that include cell cycle checkpoints and DNA repair.