1986 …2021

Research output per year

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Personal profile

Research

How DNA replication is organised and controlled to ensure precise chromosome duplication

Chromosome replication is a key event in the eukaryotic cell division cycle. During S phase the entire genome must be faithfully duplicated with the minimum of errors. The many thousands of replication forks involved in this process must be co-ordinated to ensure that despite the very large quantities of DNA involved, no section of DNA is left unreplicated and no section of DNA is replicated more than once. Cells achieve this by having a distinct stage that occurs prior to S phase when replication origins are "licensed" for replication. At the onset of S phase, replication forks are initiated only at these licensed replication origins. As initiation occurs at each origin, the licence is removed, thereby ensuring that it fires only once in each cell cycle. Mistakes made in this process may cause irreversible genetic modifications that could ultimately lead to the cells becoming cancerous. Many early stage cancer cells have lost the ability to correctly down-regulate the licensing system, suggesting that it is an important control system for cancer cells to evade.

The aim of our work is to understand at a molecular level the way that chromosome replication is regulated, and to apply this knowledge to improving  the diagnosis and treatment of cancer. We use a number of different model systems to study cell cycle control of DNA replication. Cell-free extracts of Xenopuseggs, which support all the nuclear events of the early embryonic cell cycle, provide a powerful system for studying DNA replication control at a biochemical level. We then apply insights gained from the Xenopus system to the study of replication in human tissue culture cells which have important advantages for studying DNA replication using cell biological and molecular genetic approaches. We are also using C. elegans as a model system to study DNA replication in a genuine physiological setting. Current research projects are addressing: a) how the licensing system is regulated at different stages of the cell division cycle; b) how the Cdc7 and cyclin-dependent kinases trigger the initiation of DNA replication; c) the way that replication is co-ordinated with other cell cycle events; d) how replication origins are physically organised on chromosomal DNA; and e) how different cellular stresses affect the replication programme through checkpoint signals.

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Projects

Research Output

3.0 tera-basepairs as a fundamental limit for robust DNA replication

Al Mamun, M., Albergante, L., Blow, J. & Newman, T., 22 Apr 2020, In : Physical Biology.

Research output: Contribution to journalArticle

Open Access
File
  • 20 Downloads (Pure)

    Defects in the origin licensing checkpoint stresses cells exiting G0

    Blow, J. J., 1 Jul 2019, In : Journal of Cell Biology. 218, 7, p. 2080-2081 2 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 2 Citations (Scopus)
    71 Downloads (Pure)

    Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing

    Shoaib, M., Walter, D., Gillespie, P. J., Izard, F., Fahrenkrog, B., Lleres, D., Lerdrup, M., Johansen, J. V., Hansen, K., Julien, E., Blow, J. J. & Sørensen, C. S., 12 Sep 2018, In : Nature Communications. 9, 1, p. 1-11 11 p., 3704.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 3 Citations (Scopus)
    109 Downloads (Pure)

    Lgr5+ intestinal stem cells reside in an unlicensed G1 phase

    Carroll, T., Newton, I., Chen, Y., Blow, J. & Nathke, I., 7 May 2018, In : Journal of Cell Biology. 217, 5, p. 1667-1685 19 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 6 Citations (Scopus)
    145 Downloads (Pure)

    The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1

    Barini, E., Miccoli, A., Tinarelli, F., Mulholland, K., Kadri, H., Khanim, F., Stojanovski, L., Read, K. D., Burness, K., Blow, J. J., Mehellou, Y. & Muqit, M. M. K., 2 Mar 2018, In : ChemBioChem. 19, 5, p. 425-429 5 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 11 Citations (Scopus)
    139 Downloads (Pure)

    Prizes

    British Association for Cancer Research / Zeneca "Young Scientist of the Year"

    Blow, Julian (Recipient), 1996

    Prize: Prize (including medals and awards)

    Fellow of the Academy of Medical Sciences

    Blow, Julian (Recipient), 2012

    Prize: Election to learned society

    Fellow of the Royal Society of Edinburgh

    Blow, Julian (Recipient), 2002

    Prize: Election to learned society

    Lister Institute Jenner-Centenary Research Fellow (1991-1996)

    Blow, Julian (Recipient), 1991

    Prize: Fellowship awarded competitively

    Member of the European Molecular Biology Organization

    Blow, Julian (Recipient), 1999

    Prize: Election to learned society

    Activities

    Science Saturday: Guardians of the Genome

    Amy Cameron (Organiser), , Rolf Black (Organiser), , Bettina Meier (Contributor), , Jane Wright (Contributor), , Julian Blow (Presenter), , John Eykelenboom (Presenter), , Harinath Doodhi (Presenter), , Constance Alabert (Presenter), , Elisa Garcia-Wilson (Presenter), , Vanesa Alvarez (Contributor), , Veronica Pravata (Presenter), , Susanne Bandau (Presenter), , Amanda Baizan Edge (Contributor), , Fiona Haward (Presenter), , Diana Rios Szwed (Presenter), & Carolina Gomez Moreira (Presenter)

    22 Feb 2020

    Activity: Other activity typesOther

    National University of Ireland, Galway (External organisation)

    J. Julian Blow (Chair)

    2012

    Activity: Membership typesMembership of panel

    DNA Replication of Eukaryotic Genomes

    J. Julian Blow (Invited speaker)

    2 Jul 20127 Jul 2012

    Activity: Participating in or organising an event typesParticipation in conference

    European Research Council (External organisation)

    J. Julian Blow (Member)

    2012

    Activity: Membership typesMembership of committee

    Thesis

    An investigation into the regulation of replication factories and dormant origins in human cells

    Author: McIntosh, D., 2014

    Supervisor: Blow, J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    Consequences of partial chromosome re-replication in mammalian cells

    Author: Klotz-Noack, K., 2013

    Supervisor: Blow, J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Investigating the Mechanism of Geminin Inactivation

    Author: Creavin, K., 2015

    Supervisor: Blow, J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Post-Replicative Resolution of Under-Replication

    Author: Carrington, J. T., 2017

    Supervisor: Blow, J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Spatiotemporal dynamics of cell division in intestinal homeostasis

    Author: Carroll, T. D., 2016

    Supervisor: Nathke, I. (Supervisor) & Blow, J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy