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Dr Greg Ngo
Research Fellow
- NgoG@cardiff.ac.uk
- Cancer Genetics Building, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
- Available for postgraduate supervision
Overview
R-loops & Genome Stability Lab
My current research focuses on understanding the formation of R-loops, enigmatic structures containing DNA-RNA hybrids, at DNA double strand breaks, and how this process affects genome stability.
One major project in the lab involves investigating the roles of R-loops and genome stability in the pathogenesis of neurodevelopmental disorders such as intellectual disability, autism spectrum disorder (ASD) and attention deficit hyperactive disorder (ADHD). We are mainly funded by a Wellcome Trust Career Development Award.
Publication
2022
- Parker, C. et al. 2022. BCL-3 loss sensitises colorectal cancer cells to DNA damage by targeting homologous recombination. DNA Repair 115, article number: 103331. (10.1016/j.dnarep.2022.103331)
2021
- Ngo, G. H. P., Grimstead, J. W. and Baird, D. M. 2021. UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair. Nature Communications 12, article number: 3849. (10.1038/s41467-021-24201-w)
2018
- Ngo, G., Hyatt, S., Grimstead, J., Jones, R., Hendrickson, E., Pepper, C. and Baird, D. 2018. PARP inhibition prevents escape from a telomere-driven crisis and inhibits cell immortalisation. Oncotarget 9(101), pp. 37549-37563. (10.18632/oncotarget.26499)
2017
- Wardell, K., Haldenby, S., Jones, N., Liddell, S., Ngo, G. and Allers, T. 2017. RadB acts in homologous recombination in the archaeon Haloferax volcanii, consistent with a role as recombination mediator. DNA Repair 55, pp. 7-16. (10.1016/j.dnarep.2017.04.005)
- Holstein, E., Ngo, G., Lawless, C., Banks, P., Greetham, M., Wilkinson, D. and Lydall, D. 2017. Systematic analysis of the DNA damage response network in telomere defective budding yeast. G3: Genes | Genomes | Genetics 7(7), pp. 2375. (10.1534/g3.117.042283)
2015
- Ngo, G. H. and Lydall, D. 2015. The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks. Nucleic Acids Research 43(10), pp. 5017–5032. (10.1093/nar/gkv409)
2014
- Ngo, G. H., Balakrishnan, L., Dubarry, M., Campbell, J. L. and Lydall, D. 2014. The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. Nucleic Acids Research 42(16), pp. 10516–10528. (10.1093/nar/gku746)
2011
- Addinall, S. G. et al. 2011. Quantitative fitness analysis shows that NMD proteins and many other protein complexes suppress or enhance distinct telomere cap defects. PLoS Genetics 7(4), article number: e1001362. (10.1371/journal.pgen.1001362)
2010
- Ngo, G. and Lydall, D. 2010. Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9. PLoS Genetics 6(8), article number: e1001072. (10.1371/journal.pgen.1001072)
2009
- Matic, I., Delmas, S., Shunburne, L., Ngo, H. and Allers, T. 2009. Mre11-Rad50 promotes rapid repair of DNA damage in the Polyploid Archaeon Haloferax volcanii by restraining homologous recombination. PLoS Genetics 5(7), article number: 1000552. (10.1371/journal.pgen.1000552)
- Mankouri, H. W., Ngo, G. and Hickson, I. D. 2009. Esc2 and Sgs1 Act in Functionally Distinct Branches of the Homologous Recombination Repair Pathway inSaccharomyces cerevisiae. Molecular Biology of the Cell 20(6), pp. 1683-1694. (10.1091/mbc.e08-08-0877)
2008
- Morin, I., Ngo, H. P., Greenall, A., Zubko, M. K., Morrice, N. and Lydall, D. 2008. Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage response. The EMBO Journal 27(18), pp. 2400-2410. (10.1038/emboj.2008.171)
2007
- Mankouri, H. W., Ngo, G. and Hickson, I. D. 2007. Shu proteins promote the formation of homologous recombination intermediates that are processed by sgs1-rmi1-top3. Molecular Biology of the Cell 18(10), pp. 3711-4200. (10.1091/mbc.e07-05-0490)
2004
- Allers, T., Ngo, H. P., Mevarech, M. and Lloyd, R. G. 2004. Development of Additional Selectable Markers for the Halophilic Archaeon Haloferax volcanii Based on the leuB and trpA Genes. Applied and Environmental Microbiology 70(2), pp. 943-953. (10.1128/AEM.70.2.943-953.2004)
2003
- Allers, T. and Ngo, H. 2003. Genetic analysis of homologous recombination in Archaea: Haloferax volcanii as a model organism. Biochemical Society Transactions 31(3), pp. 706-710. (10.1042/bst0310706)
- Moore, T., McGlynn, P., Ngo, H. P., Sharples, G. and Lloyd, R. 2003. The RdgC protein of Escherichia coli binds DNA and counters a toxic effect of RecFOR in strains lacking the replication restart protein PriA. The EMBO Journal 22(3), pp. 735-745. (10.1093/emboj/cdg048)
Articles
- Parker, C. et al. 2022. BCL-3 loss sensitises colorectal cancer cells to DNA damage by targeting homologous recombination. DNA Repair 115, article number: 103331. (10.1016/j.dnarep.2022.103331)
- Ngo, G. H. P., Grimstead, J. W. and Baird, D. M. 2021. UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair. Nature Communications 12, article number: 3849. (10.1038/s41467-021-24201-w)
- Ngo, G., Hyatt, S., Grimstead, J., Jones, R., Hendrickson, E., Pepper, C. and Baird, D. 2018. PARP inhibition prevents escape from a telomere-driven crisis and inhibits cell immortalisation. Oncotarget 9(101), pp. 37549-37563. (10.18632/oncotarget.26499)
- Wardell, K., Haldenby, S., Jones, N., Liddell, S., Ngo, G. and Allers, T. 2017. RadB acts in homologous recombination in the archaeon Haloferax volcanii, consistent with a role as recombination mediator. DNA Repair 55, pp. 7-16. (10.1016/j.dnarep.2017.04.005)
- Holstein, E., Ngo, G., Lawless, C., Banks, P., Greetham, M., Wilkinson, D. and Lydall, D. 2017. Systematic analysis of the DNA damage response network in telomere defective budding yeast. G3: Genes | Genomes | Genetics 7(7), pp. 2375. (10.1534/g3.117.042283)
- Ngo, G. H. and Lydall, D. 2015. The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks. Nucleic Acids Research 43(10), pp. 5017–5032. (10.1093/nar/gkv409)
- Ngo, G. H., Balakrishnan, L., Dubarry, M., Campbell, J. L. and Lydall, D. 2014. The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. Nucleic Acids Research 42(16), pp. 10516–10528. (10.1093/nar/gku746)
- Addinall, S. G. et al. 2011. Quantitative fitness analysis shows that NMD proteins and many other protein complexes suppress or enhance distinct telomere cap defects. PLoS Genetics 7(4), article number: e1001362. (10.1371/journal.pgen.1001362)
- Ngo, G. and Lydall, D. 2010. Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9. PLoS Genetics 6(8), article number: e1001072. (10.1371/journal.pgen.1001072)
- Matic, I., Delmas, S., Shunburne, L., Ngo, H. and Allers, T. 2009. Mre11-Rad50 promotes rapid repair of DNA damage in the Polyploid Archaeon Haloferax volcanii by restraining homologous recombination. PLoS Genetics 5(7), article number: 1000552. (10.1371/journal.pgen.1000552)
- Mankouri, H. W., Ngo, G. and Hickson, I. D. 2009. Esc2 and Sgs1 Act in Functionally Distinct Branches of the Homologous Recombination Repair Pathway inSaccharomyces cerevisiae. Molecular Biology of the Cell 20(6), pp. 1683-1694. (10.1091/mbc.e08-08-0877)
- Morin, I., Ngo, H. P., Greenall, A., Zubko, M. K., Morrice, N. and Lydall, D. 2008. Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage response. The EMBO Journal 27(18), pp. 2400-2410. (10.1038/emboj.2008.171)
- Mankouri, H. W., Ngo, G. and Hickson, I. D. 2007. Shu proteins promote the formation of homologous recombination intermediates that are processed by sgs1-rmi1-top3. Molecular Biology of the Cell 18(10), pp. 3711-4200. (10.1091/mbc.e07-05-0490)
- Allers, T., Ngo, H. P., Mevarech, M. and Lloyd, R. G. 2004. Development of Additional Selectable Markers for the Halophilic Archaeon Haloferax volcanii Based on the leuB and trpA Genes. Applied and Environmental Microbiology 70(2), pp. 943-953. (10.1128/AEM.70.2.943-953.2004)
- Allers, T. and Ngo, H. 2003. Genetic analysis of homologous recombination in Archaea: Haloferax volcanii as a model organism. Biochemical Society Transactions 31(3), pp. 706-710. (10.1042/bst0310706)
- Moore, T., McGlynn, P., Ngo, H. P., Sharples, G. and Lloyd, R. 2003. The RdgC protein of Escherichia coli binds DNA and counters a toxic effect of RecFOR in strains lacking the replication restart protein PriA. The EMBO Journal 22(3), pp. 735-745. (10.1093/emboj/cdg048)
Research
I have a long-standing interest in DNA repair and its contribution to genome stability, focusing on the repair of DNA double-strand breaks (DSBs) and dysfunctional telomeres. Over the past 20 years, I have developed unique expertise in the analysis of DNA repair intermediates/products and have contributed to the understanding of various DNA repair mechanisms in humans and model organisms (budding yeast, archaea, and bacteria).
More recently, I have become interested in the role of DNA-RNA hybrids in DNA repair, following my discovery that R loops accumulate at DSBs. Furthermore, I found that two genes, UPF1 and UPF3B, stimulate the formation of these enigmatic structures in human cells. Intriguingly, dysfunction in UPF1 and UPF3B is associated with an inherited risk for developing neurodevelopmental disorders.
My research goals are to establish the molecular mechanisms that promote R-loop formation at DSBs and understand how these structures affect genome stability and the development of neurodevelopmental disorders. To do this, we use a multidisciplinary approach that combines genetics, biochemistry, bioinformatics, and neuroscience. Key techniques we employ include CRISPR gene editing, quantitative amplification of single-stranded DNA (QAOS), two-dimensional DNA gel electrophoresis, single-molecule PCR amplicon analysis, next-generation sequencing (NGS), long-read nanopore sequencing, DSB mapping (INDUCE-seq), and induced pluripotent stem cell technologies.
Lab members
Dr Siamak Kamranvar
Dr Ashley Parkes
Biography
My interest in genome stability ignited during my undergraduate project, where I was studying DNA repair mutants in E. coli under the guidance of Prof. Robert Lloyd at the University of Nottingham. As a research assistant for Dr. Thorsten Allers, also at the University of Nottingham, I transitioned to working on the archaeon H. volcanii, contributing to the development of genetic tools to investigate homologous recombination (HR).
Subsequently, during my D.Phil. studies under the mentorship of Prof. Ian Hickson at the University of Oxford, I characterized genes that genetically interact with the Bloom helicase (Sgs1) in budding yeast. This research led to the identification of Esc2 as a novel factor essential for HR at stalled replication forks.
Following completion of my D.Phil., I joined the laboratory of Prof. David Lydall at Newcastle University to explore the mechanism of DNA repair at uncapped telomeres in budding yeast. My work shed light on the crucial role of DNA resection in cellular senescence, unveiling its intricate regulation by various DNA damage checkpoint proteins.
My research journey continued at Cardiff University, where I joined the laboratory of Prof. Duncan Baird to investigate telomeric DNA repair in human cells. Through my studies, I demonstrated that PARP inhibitors selectively eliminate cells during telomere crisis, presenting a promising avenue for preventing cell immortalization and impeding cancer progression. Recently, I made a ground breaking discovery by directly detecting R-loops at DNA double-strand breaks (DSBs) for the first time, revealing their generation by UPF1 to stimulate DNA repair.
In 2023, I was awarded a Wellcome Trust Career Development Award to investigate the roles of R-loops and mutations in the pathogenesis of neurodevelopmental disorders.
Supervisions
I am interested in supervising PhD students in the areas of:
- Genome stability
- DNA repair
- Neurodevelopmental disorders
