Senior Lecturer
- About
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- Email Address
- s.hiraga@abdn.ac.uk
- Telephone Number
- +44 (0)1224 437317
- Office Address
- School/Department
- School of Medicine, Medical Sciences and Nutrition
Qualifications
- BSc1990 - Osaka University
- PhD1996 - Osaka University
- FHEA2023 - Advance HE
External Memberships
Member of the following learned societies:
Biochemical Society; Genetics Society; Molecular Biology Society of Japan
Editorial board member of:
Ad hoc reviewer for international research journals:
Current Opinion in Cell Biology; Cytogenetic and Genome Research; eLife; The Journal of Biochemistry; Journal of Cell Science; Nucleic Acids Research; PLoS One
Latest Publications
Checkpoint phosphorylation sites on budding yeast Rif1 protect nascent DNA from degradation by Sgs1-Dna2
PLoS Genetics, vol. 19, no. 11, e1011044Contributions to Journals: ArticlesProtection 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: Articles
- Research
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Research Overview
My research goal is to investigate the mechanisms of chromosome maintenance, particularly those involved in the accurate and robust replication of chromosomal DNA.
My research involves yeast and human cell lines, and I identified Rif1-mediated Protein Phosphatase 1 (PP1) targeting to replication initiation proteins. I showed that RIF1-PP1 controls the initiation of DNA replication by modulating 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 researching Rif1 protein's protective role in DNA replication stress on chromosomes. (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 aim to expand our knowledge of the mechanisms that maintain integrity in human cells and develop novel approaches to cancer prevention and treatment.
We recently found that SAF-A (also known as HNRNPU) ensures robust DNA replication in human cells by regulating 3D chromatin structure as an RNA-binding and chromatin-associated protein. (Connolly et al. J Cell Sci (2022) 135 (2): jcs258991).
We are using both baker's yeast and cultured human cells as model organisms. Despite their differences in size, shape, and behavior, these cells share many fundamental mechanisms. Surprisingly, many of the genes and proteins found in our cells also exist and play similar roles in tiny yeast cells. These organisms have both advantages and drawbacks as model organisms and complement each other. I aim to combine their strengths 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 also investigating the function of human SAF-A protein in;
- Promoting replication origin licensing
- Assisting replication fork movement
- Promoting cell proliferation
I'm using both classical genetics and cutting-edge technologies such as ;
- Genetic engineering
- Flow cytometry
- 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 Jon Higgins (University of New Castle). I am also conducting international collaboration with Prof Peter Adams (Sanford Burnham Prebys), 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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- Publications
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Page 1 of 2 Results 1 to 25 of 29
Checkpoint phosphorylation sites on budding yeast Rif1 protect nascent DNA from degradation by Sgs1-Dna2
PLoS Genetics, vol. 19, no. 11, e1011044Contributions to Journals: ArticlesProtection 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.201948152
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/11048/1/embr.201846222.full.pdf
- [ONLINE] View publication in Scopus
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: PostersProtein Phosphatases and DNA Replication Initiation
The Initiation of DNA Replication in Eukaryotes. Kaplan, D. L. (ed.). Springer, pp. 461-477, 17 pagesChapters in Books, Reports and Conference Proceedings: Chapters- [ONLINE] DOI: https://doi.org/10.1007/978-3-319-24696-3_23
Molecular mechanisms of DNA replication control by mammalian RIF1 protein
EMBO conference on DNA replication, chromosome segregation and cell divisionContributions to Conferences: PostersRif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex
Genes & Development, vol. 28, no. 4, pp. 372-383Contributions to Journals: ArticlesNegative regulation of DNA replication by Rif1 through protein phosphatase PP-1
CSH Meeting "Eukaryotic DNA replication and genome maintenance"Contributions to Conferences: PostersNegative regulation of DNA replication by Rif1 through DDK
British Yeast Group Meeting 2013Contributions to Conferences: PostersTFIIIC Localizes Budding Yeast ETC Sites to the Nuclear Periphery
Molecular Biology of the Cell, vol. 23, no. 14, pp. 2741-2754Contributions to Journals: ArticlesQuantitative proteomic analysis of yeast DNA replication proteins
Methods, vol. 57, no. 2, pp. 196-202Contributions to Journals: Articles- [ONLINE] http://www.ncbi.nlm.nih.gov/pubmed/22465796
- [ONLINE] DOI: https://doi.org/10.1016/j.ymeth.2012.03.012
Quantitative proteomic analysis of chromatin reveals that Ctf18 acts in the DNA replication checkpoint
Molecular and Cellular Proteomics, vol. 10, no. 7, M110 005561Contributions to Journals: Articles- [ONLINE] http://www.ncbi.nlm.nih.gov/pubmed/21505101
- [ONLINE] DOI: https://doi.org/10.1074/mcp.M110.005561
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/2495/1/Kubota_2011.pdf
The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation
Molecular Biology of the Cell, vol. 22, no. 10, pp. 1753-1756Contributions to Journals: Articles- [ONLINE] http://www.ncbi.nlm.nih.gov/pubmed/21441303
- [ONLINE] DOI: https://doi.org/10.1091/mbc.E10-06-0549
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/2269/1/Lian_2011.pdf
Early initiation of a replication origin tethered at the nuclear periphery
Journal of Cell Science, vol. 123, pp. 1015-1019Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1242/jcs.060392
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/760/1/Ebrahimi_et_al_2010.pdf
Histone H3 lysine 56 acetylation by Rtt109 is crucial for chromosome positioning
Journal of Cell Biology, vol. 183, no. 4, pp. 641-651Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1083/jcb.200806065
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/2273/1/Hiraga_et_al_2008.pdf
OriDB: a DNA replication origin database
Nucleic Acids Research, vol. 35, no. Database Issue, pp. D40-D46Contributions to Journals: ArticlesThe Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time
EMBO Journal, vol. 25, no. 7, pp. 1505-1514Contributions to Journals: Articles- [ONLINE] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1440320/
- [ONLINE] DOI: https://doi.org/10.1038/SJ.EMBOJ.7601038
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/802/1/52667.pdf
DNA polymerases alpha, delta, and epsilon localize and function together at replication forks in Saccharomyces cerevisiae
Genes to Cells, vol. 10, no. 4, pp. 297-309Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1111/j.1365-2443.2005.00843.x