Dr Marco Saponaro PhD

Dr Marco Saponaro

Institute of Cancer and Genomic Sciences
Associate Professor

Contact details

Address
Department 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 and DNA replication are coordinated, and how in context with defective transcription this can lead to increased 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

  • Associate Professor, University of Birmingham (UK), 2021
  • 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, he characterised the role the CDK1 dependent phosphorylation of Srs2, finding that it was specifically required to promote homologous recombination in response to double strand break repair. 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). Here he got in particular interested in the interaction between the RNA Pol II and RECQL5, finding 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. The lab focuses on the characterising 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

  • Module co-lead on the MRes in Cancer Sciences, Genomics and Genome-based Therapeutics module 
  • Module co-lead on the MRes in Functional Genomics, Introduction to Bioinformatics module 
  • Module co-lead on the MSc Genomic Medicine, Epigenetics and Epigenomics module
  • Small Group Teaching in MBChB Year Two Cancer: Causes to Cure module
  • Lecturer BSc Biomedical Science Year Three: Cancer Pathogenesis and Treatment
  • Lecturer in MSc Clinical Oncology: Molecular Pathology of Cancer

Postgraduate supervision

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.

After being appointed as a Birmingham Fellow he has expanded and developed his research interests. In particular, he is characterising 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 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.

ResearchGate Profile

Publications

Recent publications

Article

Rojas, P, Wang, J, Guglielmi, G, Sadurnì, MM, Pavlou, L, Leung, GHD, Rajagopal, V, Spill, F & Saponaro, M 2024, 'Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression', Genome Biology, vol. 25, no. 1, 126. https://doi.org/10.1186/s13059-024-03278-8

Mackay, HL, Stone, HR, Ronson, GE, Ellis, K, Lanz, A, Aghabi, Y, Walker, AK, Starowicz, K, Garvin, AJ, Van Eijk, P, Koestler, SA, Anthony, EJ, Piberger, AL, Chauhan, AS, Conway-Thomas, P, Vaitsiankova, A, Vijayendran, S, Beesley, JF, Petermann, E, Brown, EJ, Densham, RM, Reed, SH, Dobbs, F, Saponaro, M & Morris, JR 2024, 'USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication', Nature Communications, vol. 15, 8102. https://doi.org/10.1038/s41467-024-52250-4

Scaramuzza, S, Jones, RM, Sadurni, MM, Reynolds-Winczura, A, Poovathumkadavil, D, Farrell, A, Natsume, T, Rojas, P, Cuesta, CF, Kanemaki, MT, Saponaro, M & Gambus, A 2023, 'TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells', Nature Communications, vol. 14, no. 1, 5071. https://doi.org/10.1038/s41467-023-40695-y

De, S, Edwards, DM, Dwivedi, V, Wang, J, Varsally, W, Dixon, HL, Singh, AK, Owuamalam, PO, Wright, MT, Summers, RP, Hossain, MN, Price, EM, Wojewodzic, MW, Falciani, F, Hodges, NJ, Saponaro, M, Tanaka, K, Azzalin, CM, Baumann, P, Hebenstreit, D & Brogna, S 2022, 'Genome-wide chromosomal association of Upf1 is linked to Pol II transcription in Schizosaccharomyces pombe', Nucleic Acids Research, vol. 50, no. 1, pp. 350-367. https://doi.org/10.1093/nar/gkab1249

Bayley, R, Borel, V, Moss, R, Sweatman, E, Ruis, P, Ormrod, A, Goula, A, Mottram, R, Stanage, T, Hewitt, G, Saponaro, M, Stewart, G, Boulton, S & Higgs, M 2022, 'H3K4 methylation by SETD1A/BOD1L facilitates RIF1-dependent NHEJ', Molecular Cell, vol. 82, no. 10, pp. 1924-1939.e10. https://doi.org/10.1016/j.molcel.2022.03.030

Saponaro, M 2022, 'Transcription–replication coordination', Life, vol. 12, no. 1, 108. https://doi.org/10.3390/life12010108

Wang, J, Rojas, P, Mao, J, Muste Sadurni, M, Garnier, O, Xiao, S, Higgs, M, Garcia, P & Saponaro, M 2021, 'Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M', Cell Reports, vol. 34, no. 7, 108759. https://doi.org/10.1016/j.celrep.2021.108759

Wang, J & Saponaro, M 2021, 'Protocol for analysis of G2/M DNA synthesis in human cells', STAR Protocols, vol. 2, no. 2, 100570. https://doi.org/10.1016/j.xpro.2021.100570

Bowry, A, Piberger, AL, Rojas, P, Saponaro, M & Petermann, E 2018, 'BET inhibition induces HEXIM1- and RAD51-dependent conflicts between transcription and replication', Cell Reports, vol. 25, no. 8, pp. 2061–2069.e4. https://doi.org/10.1016/j.celrep.2018.10.079

Comment/debate

Saponaro, M 2024, 'Adding a transcription-coupled repair pathway', Nature Cell Biology, vol. 26, no. 5, pp. 670-671. https://doi.org/10.1038/s41556-024-01399-7

Preprint

Scaramuzza, S, Muste Sadurni, M, Poovathumkadavil, D, Natsume, T, Rojas, P, Kanemaki, MT, Saponaro, M & Gambus, A 2022 'Ubiquitin ligase TRAIP plays an essential role during the S-phase of unperturbed cell cycle in the resolution of DNA replication – transcription conflicts' bioRxiv. https://doi.org/10.1101/2022.03.23.485338

De, S, Dwivedi, V, Wang, J, Edwards, DM, Varsally, W, Singh, AK, Dixon, HL, Wojewodzic, MW, Falciani, F, Hodges, NJ, Saponaro, M, Tanaka, K, Azzalin, CM, Baumann, P, Hebenstreit, D & Brogna, S 2021 'Genome-wide chromosomal association of Upf1 is linked to Pol II transcription in Schizosaccharomyces pombe' bioRxiv. https://doi.org/10.1101/2021.04.12.437332

Winczura, K, Ceylan, H, Sledziowska, M, Jones, M, Fagarasan, H, Wang, J, Saponaro, M, Arnold, R, Hebenstreit, D & Grzechnik, P 2021 'RPRD proteins control transcription in human cells' bioRxiv. https://doi.org/10.1101/2021.06.20.449126

Review article

Muste Sadurni, M & Saponaro, M 2023, 'Deregulations of RNA Pol II Subunits in Cancer', Applied Biosciences, vol. 2, no. 3, pp. 459-476. https://doi.org/10.3390/applbiosci2030029

Wang, J, Sadurni, MM & Saponaro, M 2022, 'RNAPII response to transcription‐blocking DNA lesions in mammalian cells', The FEBS journal. https://doi.org/10.1111/febs.16561

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