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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.

Our research

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?

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If an insufficient number of replication origins are activated or if replication forks collapse, genome replication may be incomplete. How does the cell respond?

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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.

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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.

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Latest updates

Recent Publications:

Donaldson, AD, Nieduszynski, CA. Genome-wide analysis of DNA replication timing in single cells: Yes! We're all individuals. Genome Biol. 2019;20 (1):111. doi: 10.1186/s13059-019-1719-y. PubMed PMID:31146781 PubMed Central PMC6541995.
Tong, P, Pidoux, AL, Toda, NRT, Ard, R, Berger, H, Shukla, M, Torres-Garcia, J, Müller, CA, Nieduszynski, CA, Allshire, RC. Interspecies conservation of organisation and function between nonhomologous regional centromeres. Nat Commun. 2019;10 (1):2343. doi: 10.1038/s41467-019-09824-4. PubMed PMID:31138803 PubMed Central PMC6538654.
Müller, CA, Boemo, MA, Spingardi, P, Kessler, BM, Kriaucionis, S, Simpson, JT, Nieduszynski, CA. Capturing the dynamics of genome replication on individual ultra-long nanopore sequence reads. Nat. Methods. 2019;16 (5):429-436. doi: 10.1038/s41592-019-0394-y. PubMed PMID:31011185 .
Bazarova, A, Nieduszynski, CA, Akerman, I, Burroughs, NJ. Bayesian inference of origin firing time distributions, origin interference and licencing probabilities from Next Generation Sequencing data. Nucleic Acids Res. 2019;47 (5):2229-2243. doi: 10.1093/nar/gkz094. PubMed PMID:30859196 PubMed Central PMC6412128.
Oldach, P, Nieduszynski, CA. Cohesin-Mediated Genome Architecture Does Not Define DNA Replication Timing Domains. Genes (Basel). 2019;10 (3):. doi: 10.3390/genes10030196. PubMed PMID:30836708 PubMed Central PMC6471042.
Batrakou, DG, Heron, ED, Nieduszynski, CA. Rapid high-resolution measurement of DNA replication timing by droplet digital PCR. Nucleic Acids Res. 2018;46 (19):e112. doi: 10.1093/nar/gky590. PubMed PMID:29986073 PubMed Central PMC6212846.