Our lab studies molecular pathways that regulate the replication of genomic DNA in conditions of genotoxic stress. These pathways belong to a complex signaling and response network, which works to avoid the replication of damaged DNA regions and coordinates this process with DNA repair machinery. The underlying mechanisms are critical for exact transmission of genetic information through succession of cell divisions and prevent the occurrence of replicative stress related genetic instability that can lead to development of cancers.
Our specific interest lies in the regulation of the replicative Cdc45 -MCM2-7 - GINS (CMG) helicase – an 11 subunit complex, which uses the energy from ATP hydrolysis for unwinding the double stranded template DNA in front of the progressing replisome. Assembly and activation of the CMG complex are tightly coordinated critical events, which control the initiation of genomic DNA replication, determine its exact start sites in the genomic DNA, and the precise timing in the cell cycle. Because of this, the CMG helicase is an important target of the normal cell cycle as well as the stress response pathways. Using both the biochemistry and cell biology tools, our aim is to identify and characterize the stress response factors that could operate through the direct interactions and/or modifications of the CMG helicase. We are examining the effects and possible downstream pathways related to several known stress factors, such as the checkpoint kinases, and are working on the identification of new potential candidates for such regulatory factors in the eukaryotes.
ivar.ilves [ät] ut.ee