The Cimprich lab is focused on understanding how cells maintain genomic stability, with an emphasis on the DNA damage response (DDR). This is a complex, multi-faceted response that requires cells to sense the presence of DNA damage within the genome, as well as to “choose” and coordinate a range of downstream events and outcomes. These include effects on DNA repair, transcription, and DNA replication, as well as cell cycle arrest, apoptosis, and senescence.
They are particularly interested in understanding how DNA damage is identified and resolved during DNA replication, when the genome is particularly vulnerable due to stalling of the replication fork at naturally arising and induced DNA lesions, structures or protein-DNA complexes. Stalled replication forks are unstable and can be processed in aberrant ways, leading to double-strand break formation, which is known to drive chromosomal translocation and rearrangements in cancer cells. Indeed, replication stress, a result of slowing replication fork progression, is commonly observed in cancer cells due to loss of the DDR or oncogene activation.
The lab studies the DDR using cultured mammalian cells, as well as cell-free extracts derived from the eggs of the frog Xenopus laevis together with a variety of techniques. Their goal is to understand how the DDR is initiated, how this pathway is integrated with the processes of DNA replication and transcription, and how cells recover from DNA damage.