DNA Replication Group

Research projects

Initiation of DNA replication

Initiation of DNA replication

Mapping DNA replication origins

The sites of DNA replication initiation, called replication origins, are spatially and temporally regulated. We have mapped the sites and characteristics of replication origins across the genome of several model organisms.

A global profile of replicative polymerase usage
Yasukazu Daigaku, Andrea Keszthelyi, Carolin A Müller, Izumi Miyabe, Tony Brooks, Renata Retkute, Mike Hubank, Conrad A Nieduszynski, Antony M Carr
Nature Structural & Molecular Biology   ·   09 Feb 2015   ·   doi:10.1038/nsmb.2962
Accelerated growth in the absence of DNA replication origins
Michelle Hawkins, Sunir Malla, Martin J. Blythe, Conrad A. Nieduszynski, Thorsten Allers
Nature   ·   01 Nov 2013   ·   doi:10.1038/nature12650
Conservation of replication timing reveals global and local regulation of replication origin activity
Carolin A. Müller, Conrad A. Nieduszynski
Genome Research   ·   05 Jul 2012   ·   doi:10.1101/gr.139477.112
DNA replication dynamics

DNA replication dynamics

From initiation, to fork direction and finally termination

Genomes are replicated with characteristic temporal dynamics: some regions tend to replicate early in S phase whereas others tend to replicate later. We have measured replication dyanamics, discovered regulatory mechanisms and determined the consequences of perturbed replication dynamics.

Cohesin-Mediated Genome Architecture Does Not Define DNA Replication Timing Domains
Phoebe Oldach, Conrad A. Nieduszynski
Genes   ·   04 Mar 2019   ·   doi:10.3390/genes10030196
DNA replication timing influences gene expression level
Carolin A. Müller, Conrad A. Nieduszynski
Journal of Cell Biology   ·   24 May 2017   ·   doi:10.1083/jcb.201701061
Kinetochores Coordinate Pericentromeric Cohesion and Early DNA Replication by Cdc7-Dbf4 Kinase Recruitment
Toyoaki Natsume, Carolin A. Müller, Yuki Katou, Renata Retkute, Marek Gierliński, Hiroyuki Araki, J. Julian Blow, Katsuhiko Shirahige, Conrad A. Nieduszynski, Tomoyuki U. Tanaka
Molecular Cell   ·   01 Jun 2013   ·   doi:10.1016/j.molcel.2013.05.011
Replication fork progression

Replication fork progression

Difficult to replicate sequences

Genome replication is remarkably accurate and processive. However, some regions of the genome are more difficult to replicate. This can result in replication fork pausing and the potential for genome instability, for example from fork collapse or incomplete genome replication.

Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts
Timothy J. Newman, Mohammed A. Mamun, Conrad A. Nieduszynski, J. Julian Blow
Nucleic Acids Research   ·   19 Aug 2013   ·   doi:10.1093/nar/gkt728
Synthetic genomes

Synthetic genomes

Designing stable synthetic chromosomes

The Sc2.0 project has successfully synthesised all 16 native chromosomes in Saccharomyces cerevisiae. As part of this international collaboration, we have contributed to the design of synthetic chromosomes to ensure that they are faithfully replicated in cells.

Design, construction, and functional characterization of a tRNA neochromosome in yeast
Daniel Schindler, Roy S.K. Walker, Shuangying Jiang, Aaron N. Brooks, Yun Wang, ..., Romain Koszul, Junbiao Dai, Lars M. Steinmetz, Jef D. Boeke, Yizhi Cai
Cell   ·   01 Nov 2023   ·   doi:10.1016/j.cell.2023.10.015
Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome
Yue Shen, Yun Wang, Tai Chen, Feng Gao, Jianhui Gong, ..., Junbiao Dai, Jef D. Boeke, Xun Xu, Yizhi Cai, Huanming Yang
Science   ·   10 Mar 2017   ·   doi:10.1126/science.aaf4791
Genome sequencing

Genome sequencing

Completing genomes

The power of genomic technologies are built upon high quality complete reference genome sequences. We have contributed to a series of high quality telomere-to-telomere genome sequences.

Schizosaccharomyces versatilis represents a distinct evolutionary lineage of fission yeast
Graham J. Etherington, Elisa Gomez Gil, Wilfried Haerty, Snezhana Oliferenko, Conrad A. Nieduszynski
Yeast   ·   26 Dec 2023   ·   doi:10.1002/yea.3919
Interspecies conservation of organisation and function between nonhomologous regional centromeres
Pin Tong, Alison L. Pidoux, Nicholas R. T. Toda, Ryan Ard, Harald Berger, Manu Shukla, Jesus Torres-Garcia, Carolin A. Müller, Conrad A. Nieduszynski, Robin C. Allshire
Nature Communications   ·   28 May 2019   ·   doi:10.1038/s41467-019-09824-4
Genomic technologies

Genomic technologies

From populations to single molecules

We have developed a series of innovative genomic technolgies to determine DNA replication dynamics. Both population-level and single molecule approaches have allowed discovery of sites of replication initiation and subsequent replication dynamics.

DNA copy-number measurement of genome replication dynamics by high-throughput sequencing: the sort-seq, sync-seq and MFA-seq family
Dzmitry G. Batrakou, Carolin A. Müller, Rosemary H. C. Wilson, Conrad A. Nieduszynski
Nature Protocols   ·   12 Feb 2020   ·   doi:10.1038/s41596-019-0287-7
Capturing the dynamics of genome replication on individual ultra-long nanopore sequence reads
Carolin A. Müller, Michael A. Boemo, Paolo Spingardi, Benedikt M. Kessler, Skirmantas Kriaucionis, Jared T. Simpson, Conrad A. Nieduszynski
Nature Methods   ·   22 Apr 2019   ·   doi:10.1038/s41592-019-0394-y