Radiation exposure promotes genotoxic damage, causing wholesale chromosomal alterations that jeopardize viability and/or reproductive capacity. Consequently, all organisms have evolved sophisticated mechanisms that respond to and counteract these effects. In eukaryotes, radiation responses can be divided into three functional categories: the damage sensors, the signal transmitters, and the effectors. Sensors must have the ability to discriminate damaged from normal DNA and must show a defect in one or more damage responses when mutated. A current model for the sensors in S. pombe describes a multi-component complex that is recruited to replication forks that are stalled at damaged DNA by R17 associated replication factor C (RFC). As a metazoan, Drosophila offers fundamental insights regarding the ways in which developmental programs specify outcomes and exert constraints upon adaptive responses to radiation damage. Drosophila orthologs of these S. pombe's genes may, likewise, be recruited to stalled replication at damaged DNA via the RFC and are reasonable candidates for damage sensors. Once DNA damage is recognized, signal transmitters including the ATM and ATR kinases are activated. In mammals, ATM responds exclusively to ionizing radiation (IR), whereas ATR responds to IR, UV radiation, and stalled replication forks. A Drosophila ATM/ATR homolog, mei-41, was isolated as a meiotic mutant four decades ago and has been well characterized as a pleiotropic locus affecting DNA repair, chromosome instability, and defective replication control.
|Original language||English (US)|
|Title of host publication||Handbook of Cell Signaling, 2/e|
|Number of pages||5|
|State||Published - Dec 1 2010|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)