DNA replication & genome stability
The Nieduszynski lab is based at the Dunn School, University of Oxford. We are interested in understanding how cells faithfully complete genome replication. To achieve this we use cutting-edge cellular, molecular, genomic, bio-informatic and mathematical modelling approaches in a variety of model systems. Ultimately, we are motivated to understand the basic biology that underpins cell growth and division.
All cells contain a complete copy of the organism’s DNA, the genetic blueprint of life, packaged into discrete units called chromosomes. Since new cells need a copy of the genetic material, the chromosomes must be completely and accurately replicated before the cell can divide. Our research aims to determine how cells ensure that the replication of each chromosome is completed before cell division. Select a tab below to learn more.
DNA replication initiates at thousands of specific sites, called DNA replication origins, distributed throughout the genome. Faithful completion of genome replication requires sufficient, appropriately distributed origins to be activated (‘fired’). We aim to discover how the cell regulates the ‘firing’ of these origins?
If an insufficient number of replication origins are activated or if replication forks collapse, genome replication may be incomplete. How does the cell respond?
Genomes are replicated in a reproducible temporal order; some regions replicate at the start of S phase, others later. We have discovered that this temporal control is of physiologically importance.
We have developed and continue to develop cutting edge technologies, from high-throughput sequencing to synthetic chromosomes. These approaches have allowed us to make fundamental discoveries about how genomes replicate in the three domains of life: bacteria, archaea and eukaryotes.