Dr Marco Saponaro PhD

Dr Marco Saponaro

Institute of Cancer and Genomic Sciences
Birmingham Fellow

Contact details

Address
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Dr Saponaro is interested in characterising mechanisms of genome stability maintenance. In particular he is interested in understanding how RNA Pol II transcription, especially when in mutant contexts that affect transcription progression, can induce genome instability. He develops his research combining whole genome analyses with functional studies. He characterises RNA Pol II progression identifying how it is affected in mutant contexts, correlating transcription problems with the sites of genome instability. All these allow identifying the mechanisms of transcription-induced genome instability.
He is also interested in the relevance for human health of transcription-associated genome instability, identifying instances where these problems arise and approaches to exploit therapeutically these situations.

Qualifications

  • Birmingham Fellow, University of Birmingham (UK), 2015
  • PhD in Molecular Medicine, University of Milan (Italy) 2009
  • MSc (Hons) in Medical Biotechnology, University of Bologna (Italy), 2004 

Biography

After completing his MSc in Medical Biotechnology at the University of Bologna, Dr Saponaro joined the IFOM-IEO Campus in Milan for his PhD in the Foiani group. During this period the main focus of his research was the characterisation of the CDK1 dependent phosphorylation of Srs2. He found that this modification was specifically required to promote homologous recombination in response to double strand break repair, identifying Srs2 as one of the first CDK1-dependent targets in double strand break repair in yeast. Towards the end of this period Dr Saponaro developed also an interest for transcription-associated genome instability that let him to join the Svejstrup group in Clare Hall (CRUK-London Research Institute). He got in particular interested in the interaction between the RNA Pol II and RECQL5.

Characterising in deep details the relevance of this interaction, he found that RECQL5 controls the elongation rate of the RNA Pol II, reducing in this way pausing/stalling instances (transcription stress) of the RNA Pol II. These transcription stress sites turn out to be particularly detrimental for the cells, because these sites overlap with the sites of genome instability arising without RECQL5. In this way he proved how mechanistically RECQL5 roles in controlling transcription progression are connected to its roles in preserving genome stability.

After his postdoc in London he decided to move to Birmingham to establish his own lab after being awarded a Birmingham Fellowship. Main focus of his lab is to continue to characterise how transcription-associated factors promote RNA Pol II transcription and how their role is fundamental to preserve genome stability. He has also a clear interest in understanding the impact of the deregulation of transcription-associated factors in human health (in particular in cancer) and in identifying approaches to exploit these conditions for therapeutic purposes.  

Teaching

  • Small Group Teaching in MBChB Year Two Cancer: Causes to Cure module
  • Lecturer in BMedSci Year Three: DNA damage pathways in human disease module
  • Lecturer BSc Biomedical Science Year Three: Cancer Pathogenesis and Treatment
  • Lecturer in MSc Clinical Oncology: Molecular Pathology of Cancer

Research

Throughout his research career, Dr Saponaro has focused on studying and characterising genome stability maintenance, using several biological systems and techniques. During his PhD in the Foiani lab he characterised the relevance of the CDK1-dependent phosphorylation of the DNA helicase Srs2, discovering that Srs2 is one of the first identified targets of CDK1 in the double strand break repair in S. cerevisiae. He has also been involved in the characterisation of the role of Sen1 (homolog of SETX, mutated in the neurodegenerative disorders AOA2 and ALS4) in genome stability maintenance and in its role in coordinating transcription and replication.

He has been recently appointed as a Birmingham Fellow to expand and develop his research interests. In particular he wants to characterise now how and why RNA Pol II transcription can become source of genomic stress, implementing and expanding the genome wide approaches he currently uses. The interface between transcription and genomic instability in higher eukaryotes is an emerging field, with many open questions. The research program will aim not only to describe a phenotype, but also to understand the mechanism behind it. These studies will help in particular clarifying how the two biological fundamental processes of transcription and replication can coexist, how they are coordinated and how they impact on each other. This is not only a fundamental biological problem, but has clear implications for human health.

Publications

Williamson L., Saponaro M., Boeing S., East P., Mitter R., Kantidakis T., Kelly G.P., Lobley A., Walker J., Spencer-Dene B., Howell M., Stewart A., Svejstrup J.Q. UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene, Cell 2017 Feb 23 Volume 168, Issue 5, p843–855.e13 doi: 10.1016/j.cell.2017.01.019.

Kantidakis T., Saponaro M., Mitter R., Horswell S., Kranz A., Boeing S., Aygun O., Kelly G. P., Matthews N., Stewart A., Stewart A. F., and Svejstrup J. Q. Mutation of cancer driver MLL2 results in transcription stress and genome instability, Genes and Development 2016 February 15. doi: 10.1101.

Godin-Heymann N., Brabetz S., Murillo M. M., Saponaro M., Santos C. R., Lobley A., East P., Chakravarty P., Matthews N., Kelly G., Jordan S., Castellano E and Downward J. Tumour-suppression function of KLF12 through regulation of anoikis, Oncogene 2015 Oct 12. doi: 10.1038.

Saponaro M., Kantidakis T., Mitter R., Kelly G. P., Heron M., Williams H., Soeding J., Stewart A., and Svejstrup J. Q. RECQL5 Controls Transcript Elongation and Suppresses Transcription-Associated Genome Instability, Cell 2014 May 22;157(5):1037-49

Alzu A., Bermejo R., Begnis M., Lucca C., Piccini D., Carotenuto W., Saponaro M., Brambati A., Cocito A., Foiani M. and Liberi G. Senataxin associated with replication forks to proect fork integrity across RNA polymerase II-transcribed genes, Cell 2012 Nov 9; 151(4):835-46

Wilson M.D., Saponaro M., Leidl M.A. and Svejstrup JQ. MultiDsk: A Ubiquitin-Specific Affinity Resin, PLOS ONE 2012 Oct 3;

Saponaro M., Callahan D., Zheng X., Krejci L., Haber J., Klein H. and Liberi G. Cdk1 Targets Srs2 to Complete Synthesis-Dependent Strand Annealing and to Promote Recombinational Repair, PLOS Genetics 2010 Feb 26; 6(2):e1000858

Chiolo I., Saponaro M., Baryshnikova A., Kim J. H., Y. S. Seo, Liberi G. The Human F-Box DNA Helicase FBH1 Faces Saccharomyces cerevisiae Srs2 and Postreplication Repair Pathway Roles, Mol. Cell. Biol.Nov 2007; 27 (21) p 7439-7450

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