In higher organisms little is known about the checkpoint mechanisms that trigger cell cycle arrest and programmed
cell death, largely due to the absence of a genetic system. My current research centers on the development of such
a genetic system to study DNA damage induced cell cycle arrest and apoptosis in a multicellular system. Towards
that direction, we found that the germ line of C elegans has ideal properties.
We found that germ cells can both halt cell cycle progressing and induce apoptosis in response to gamma radiation
in a dose-dependent manner. Given the above results, it was reasonable to predict that genes might exist that sense
DNA damage and transmit this information to cause cell cycle arrest or apoptosis. Upon screening through a panel
of existing candidate mutations, we indeed found one mutation (rad-5 mn159), which inhibits radiation induced
cell cycle arrest and cell death. The aim of the proposal is the cloning of the rad-5 gene. Furthermore, it is planed
to perform large-scale genetic screens to isolate further mutations defective in DANN-damage triggered cell-cycle
arrest and apoptosis.