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?

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.

Latest updates

Recent Publications:

  1. 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.
  2. Wallis, ABA, Nieduszynski, CA. Investigating the role of Rts1 in DNA replication initiation. Wellcome Open Res. 2018;3 :23. doi: 10.12688/wellcomeopenres.13884.1. PubMed PMID:29721551 PubMed Central PMC5897792.
  3. Ausiannikava, D, Mitchell, L, Marriott, H, Smith, V, Hawkins, M, Makarova, KS, Koonin, EV, Nieduszynski, CA, Allers, T. Evolution of Genome Architecture in Archaea: Spontaneous Generation of a New Chromosome in Haloferax volcanii. Mol. Biol. Evol. 2018;35 (8):1855-1868. doi: 10.1093/molbev/msy075. PubMed PMID:29668953 PubMed Central PMC6063281.
  4. Kedziora, S, Gali, VK, Wilson, RHC, Clark, KRM, Nieduszynski, CA, Hiraga, SI, Donaldson, AD. Rif1 acts through Protein Phosphatase 1 but independent of replication timing to suppress telomere extension in budding yeast. Nucleic Acids Res. 2018;46 (8):3993-4003. doi: 10.1093/nar/gky132. PubMed PMID:29529242 PubMed Central PMC5934629.
  5. Müller, CA, Nieduszynski, CA. DNA replication timing influences gene expression level. J. Cell Biol. 2017;216 (7):1907-1914. doi: 10.1083/jcb.201701061. PubMed PMID:28539386 PubMed Central PMC5496624.

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Who We Are:

Group pictures

Lab Christmas dinner (Dec 2017)
Lab away day (Sept 2017)
Lab punt trip (July 2017)
Picnic in the park (July 2017)