Accurate chromosomal DNA replication is of fundamental importance for cellular function, genome integrity and development. In response to replication perturbations, DNA damage response (DDR) and DNA damage tolerance (DDT) pathways become activated and are crucial for detection and tolerance of lesions, as well as for replication completion and chromosome structural integrity. While important functions and key players of these regulatory processes have been outlined, much less is known about the choreography and mechanistic interplay between them. Moreover, the principles by which they uniquely or commonly affect replication-associated chromosome integrity and chromosome structure remain poorly understood.
Our research spans three major areas:
We are using budding yeast, vertebrate (avian DT40 cells) and mammalian cellular models, and employ genetic, molecular, biochemical and proteomic-based experimental strategies.