DNA replication & genome stability group

The group is based at The Earlham Institute on the Norwich Research Park. 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:

  • Prusokas, A, Hawkins, M, Nieduszynski, CA, Retkute, R. Effectiveness of glass beads for plating cell cultures. Phys Rev E. 2021;103 (5-1):052410. doi: 10.1103/PhysRevE.103.052410. PubMed PMID:34134194 .
  • Cooke, SL, Soares, BL, Müller, CA, Nieduszynski, CA, Bastos de Oliveira, FM, de Bruin, RAM. Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation. J Biol Chem. ;296 :100533. doi: 10.1016/j.jbc.2021.100533. PubMed PMID:33713703 PubMed Central PMC8054192.
  • Hoggard, T, Müller, CA, Nieduszynski, CA, Weinreich, M, Fox, CA. Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early- and late-replicating euchromatin. Proc Natl Acad Sci U S A. 2020;117 (25):14314-14321. doi: 10.1073/pnas.2004664117. PubMed PMID:32513739 PubMed Central PMC7322022.
  • Boemo, MA, Cardelli, L, Nieduszynski, CA. The Beacon Calculus: A formal method for the flexible and concise modelling of biological systems. PLoS Comput Biol. 2020;16 (3):e1007651. doi: 10.1371/journal.pcbi.1007651. PubMed PMID:32150540 PubMed Central PMC7082070.
  • Batrakou, DG, Müller, CA, Wilson, RHC, Nieduszynski, CA. DNA copy-number measurement of genome replication dynamics by high-throughput sequencing: the sort-seq, sync-seq and MFA-seq family. Nat Protoc. 2020;15 (3):1255-1284. doi: 10.1038/s41596-019-0287-7. PubMed PMID:32051615 .
  • 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.

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Who We Are:

Group pictures

Lab Christmas dinner (Dec 2017)
Lab away day (Sept 2017)