Andrew Bowman

Dr Andrew Bowman, Associate Professor

My interests lie in how eukaryotic DNA is packaged and organised within the cell with a recent emphasis on the spatial dynamics of interphase chromatin. As many nuclear processes require access to the genome to exert their function, such as transcription, DNA replication & DNA repair, knowing how DNA is packaged, and how chromatin can reposition itself is critical in understanding how the cell works.

Plain English

Whilst a building is made of many different materials, such as bricks, mortar, steel and glass, it is very much more that a sum of its parts. Each component has to be fabricated and placed at a defined location at a specific time in order to produce a functional structure. Similarly, a genome has multiple components, such as DNA (the genetic blueprint), proteins and RNA, all of which have to be synthesised and assembled according to very precise guidelines. My research focuses on how core components of the genome – called histones – are assembled onto DNA to create the basal level of genome organisation called ‘chromatin’.

Until now it has been difficult to observe the assembly process as it occurs in cells, and we have had to base much of our hypotheses on observing the end product. This is like trying to understand the internal architecture of a building by looking at it from the outside - it would be much more informative to have a time-lapse video showing all the different stages of construction. My aim is to develop methods so that we can see the individual stages of chromatin construction as they occur in the cell.

Studying such dynamic processes as they happen is important as dynamic rearrangements in chromatin structure and composition underlie numerous pathological conditions and govern responses to developmental and environmental cues.

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Dr Andrew Bowman, Associate Professor

Wellcome-Warwick Quantitative Biomedicine ProgrammeLink opens in a new window

PubMed

Lab website

Plain English

Summary

My main interest is focused on how eukaryotic DNA is packaged and organised within the cell. In particular, I am interested in how the core histones are assembled into nucleosomes to create a platform for higher order chromatin structure. As many nuclear processes require access to the genome to exert their function, such as transcription, DNA replication & DNA repair, correct assembly and disassembly of chromatin structure is imperative for proper cellular function.

Key to the chromatin assembly process is a set of histone specific chaperoning proteins that govern histone folding, storage and incorporation into chromatin. These are very dynamic processes, with histones being incorporated into chromatin within minutes of being synthesised in the cytoplasm. During this time it is thought that histones are transferred between a number of different chaperoning and histone modifying proteins in a maturation process that produces deposition-competent histones.

I am interested in observing such transitions in living cells using the core histone H3 and H4 as models for chromatin assembly. In order to visualise and quantify such dynamic behaviour in living cells I am developing methods that interface synthetic biology and protein engineering tools with state of the art live cell imaging approaches.

It is hoped that being able to visualise these processes in real-time will broaden our understanding of one of the most fundament processes in chromatin biology.

Selected publications:

Mamar, H., Fajka-Boja, R., Mórocz, M., Jurado, E.P., Zentout, S., Mihuţ, A., Kopasz, A.G., Mérey, M., Smith, R., Sharma, A.B., Lakin, N.D., Bowman, A.J., Haracska, L., Huet, S., Timinszky, G., (2024). The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity. Nucleic Acids Res. https://doi.org/10.1093/nar/gkae439

Pardal A.J. & Bowman A.J. (2022). A specific role for Importin-5 and NASP in the import and nuclear hand-off of monomeric H3. eLife. e81755. doi: 10.7554/eLife.81755Link opens in a new window

Pardal A.J., Fernandes-Duarte F., Bowman A.J. (2019). The histone chaperoning pathway: from ribosome to nucleosome. Essays Biochem. 63(1):29-43.Link opens in a new window Review

Apta-Smith M.J., Hernandez-Fernaud J.R., Bowman A.J. (2018). Evidence for the nuclear import of histones H3.1 and H4 as monomers. EMBO J. doi:10.15252/embj.201798714Link opens in a new window

Bowman A. et al., (2017). "sNASP and ASF1A function through both competitive and compatible modes of histone binding." Nucleic Acids Res. (2017) 45(2):643-656Link opens in a new window

Bowman A, Lercher L, Singh HR, Zinne D, Timinszky G, Carlomagno T3 Ladurner AG. (2016). "The histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats." Nucleic Acids Res 44(7):3105-17.Link opens in a new window

Bowman, A., C. M. Hammond, A. Stirling, R. Ward, W. Shang, H. El-Mkami, D. A. Robinson, D. I. Svergun, D. G. Norman and T. Owen-Hughes (2014). "The histone chaperones Vps75 and Nap1 form ring-like, tetrameric structures in solution." Nucleic Acids Res 42(9): 6038-6051.Link opens in a new window

Hondele, M., T. Stuwe, M. Hassler, F. Halbach, A. Bowman, E. T. Zhang, B. Nijmeijer, C. Kotthoff, V. Rybin, S. Amlacher, E. Hurt and A. G. Ladurner (2013). "Structural basis of histone H2A-H2B recognition by the essential chaperone FACT." Nature 499(7456): 111-114Link opens in a new window.

Bowman, A. and T. Owen-Hughes (2012). "Sulfyhydryl-reactive site-directed cross-linking as a method for probing the tetrameric structure of histones H3 and H4." Methods Mol Biol 833: 373-387.Link opens in a new window

Bowman, A., R. Ward, N. Wiechens, V. Singh, H. El-Mkami, D. G. Norman and T. Owen-Hughes (2011). "The histone chaperones Nap1 and Vps75 bind histones H3 and H4 in a tetrameric conformation." Mol Cell 41(4): 398-408.Link opens in a new window

Bowman, A., R. Ward, H. El-Mkami, T. Owen-Hughes and D. G. Norman (2010). "Probing the (H3-H4)2 histone tetramer structure using pulsed EPR spectroscopy combined with site-directed spin labelling." Nucleic Acids Res 38(2): 695-707.Link opens in a new window