Dr Shin-Ichiro Hiraga
Telephone

Dr Shin-Ichiro Hiraga
Senior Lecturer
- About
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Institute of Medical Sciences
School of Medicine, Medical Sciences & Nutrition
University of Aberdeen
Foresterhill
Aberdeen AB25 2ZD
Scotland
United Kingdom
Office:
Room 2:18
Ext. (43)7317
Lab:
Room 2:01
(43)7312
External Memberships
Member of the Genetics Society
Member of the Molecular Biology Society of Japan
Latest Publications
Protection of nascent DNA at stalled replication forks is mediated by phosphorylation of RIF1 intrinsically disordered region
eLife, vol. 11, e75047Contributions to Journals: ArticlesSAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication
Journal of Cell Science, vol. 135, no. 2, jcs.258991Contributions to Journals: ArticlesProtein phosphatase 1 acts as a RIF1 effector to suppress DSB resection prior to Shieldin action
Cell Reports, vol. 36, no. 2, 109383Contributions to Journals: ArticlesReplication timing maintains the global epigenetic state in human cells
Science, vol. 372, no. 6540, pp. 371-378Contributions to Journals: ArticlesThe RIF1-Long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress
eLife, vol. 9, e58020Contributions to Journals: Articles
- Research
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Research Overview
My research goal is to understand the mechanism of chromosome maintenance, with a focus on pathways needed for accurate and robust replication of chromosomal DNA.
Using both yeast and human cell lines, I have made important contributions in this research area, in particular the identification of Rif1-mediated Protein Phosphatase 1 (PP1) targeting to replication initiation proteins. I have demonstrated RIF1-PP1 controls the initiation of DNA replication via modulation of the phosphorylation status of MCM proteins in yeast (Hiraga et al. 2014 Genes & Development 28: 372-383) and human cells (Hiraga et al. 2017 EMBO Reports 18: 403-419).
Our group is also conducting research on how Rif1 protein protects chromosomes from damage during DNA replication stress (Hiraga et al. 2018 EMBO Reports 19: e46222; Garzon et al. 2019 Cell Reports 27: 2558-2566; Watts et al. eLife 2020;9:e58020). These projects are expected to broaden our understanding of the mechanism ensuring integrity in human cells, and develop new methods to prevent and cure cancers.
We also recently discovered that Scaffold-attachment factor A (SAF-A; also known as HNRNPU), which is known to be an RNA-binding and chromatin-associated protein that regulates 3D chromatin structure, ensures robust DNA replication in human cells (Connolly et al. J Cell Sci (2022) 135 (2): jcs258991).
We are using both baker's yeast and cultured human cells as model organisms. These cells share many fundamental mechanisms, despite they look very different in size, shape, and behaviour (and you will be surprised many of genes/proteins found in our cells also exist and play similar roles in tiny yeast cells). These organisms have both "pros" and "cons" as model organisms, and complement each other. I aim to gather strengths together from them to perform good research.
Research Areas
Research Specialisms
- Biomedical Sciences
- Biochemistry
- Molecular Biology
- Cell Biology
- Genomics
Our research specialisms are based on the Higher Education Classification of Subjects (HECoS) which is HESA open data, published under the Creative Commons Attribution 4.0 International licence.
Current Research
I am currently investigating the function of yeast and human RIF1 protein in:
- DNA replication
- Cellular response to replication stress
- Cell proliferation
- Protection of chromosomes from damage during DNA replication stress
I'm using both classical genetics and cutting-edge technologies such as ;
- Genetic engineering
- Genomics
- Proteomics
- Genome-wide ChIP
- Single-cell replication timing analysis
- Super-resolution microscopy
Collaborations
I am currently playing an important role in a collaboration involving Prof. Anne Donaldson (University of Aberdeen), Dr Tony Ly and Prof. Angus Lamond (University of Dundee), Dr Simon Boulton (Crick Institute) and Prof. Peter Adams (Cancer Research UK Beatson Institute, University of Glasgow) in which we have carried out a proteomic examination of senescent human chromatin. I am also conducting international collaboration with Dr Ichiro Hiratani (RIKEN Center for Biosystems Dynamics Research, Japan), Dr Masato Kanemaki (National Institute of Genetics, Japan), Professor Chikashi Obuse (Osaka University, Japan) and Professor Katsuhiko Shirahige (University of Tokyo, Japan).
Funding and Grants
Daiwa Anglo-Japanese Foundation Small Grant 2019
Cancer Research UK Programme Award (£1,561,000) ‘How does Rif1 regulate DNA replication and cell recovery after chemotherapeutic replication inhibition?' Grant to Prof Anne Donaldson & Dr Shin-ichiro Hiraga
Friends of ANCHOR Pilot Research Funding 2022 'How Cancer cells multiply and frow: the role of SAF_A variant proteins in cell proliferation in cancer'
- Teaching
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Teaching Responsibilities
Course co-ordinator for Honours Advanced Molecular Biology MB4050.
Contribute to;
- BC4314 Honours Biochemistry
- MB5518 Research Tutorials
- Publications
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Page 1 of 3 Results 1 to 10 of 28
Protection of nascent DNA at stalled replication forks is mediated by phosphorylation of RIF1 intrinsically disordered region
eLife, vol. 11, e75047Contributions to Journals: ArticlesSAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication
Journal of Cell Science, vol. 135, no. 2, jcs.258991Contributions to Journals: ArticlesProtein phosphatase 1 acts as a RIF1 effector to suppress DSB resection prior to Shieldin action
Cell Reports, vol. 36, no. 2, 109383Contributions to Journals: ArticlesReplication timing maintains the global epigenetic state in human cells
Science, vol. 372, no. 6540, pp. 371-378Contributions to Journals: ArticlesThe RIF1-Long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress
eLife, vol. 9, e58020Contributions to Journals: ArticlesHuman RIF1-Protein Phosphatase 1 Prevents Degradation and Breakage of Nascent DNA on Replication Stalling
Cell Reports, vol. 27, no. 9, pp. 2558-2566.e4Contributions to Journals: ArticlesBudding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks
EMBO reports, vol. 19, no. 9, e46222Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.15252/embr.201846222
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/11048/1/embr.201846222.full.pdf
Rif1 acts through Protein Phosphatase 1 but independent of replication timing to suppress telomere extension in budding yeast
Nucleic Acids Research, vol. 46, no. 8, pp. 3993-4003Contributions to Journals: ArticlesHuman RIF1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress origin activation
EMBO reports, vol. 18, no. 3, pp. 403-419Contributions to Journals: ArticlesPositive and negative control of DNA replication by human RIF1 protein: A safeguard mechanism
10th 3R International SymposiumContributions to Conferences: Posters