Ph.D., 1995, University of Padua, Italy
Research Interests
Our laboratory focuses on the mechanisms of DNA replication and repair, and on the possible strategies to target these mechanisms for cancer treatment. Aberrant DNA replication is one of the leading causes of mutations and chromosome rearrangements associated with several cancer related pathologies. At the same time, agents that stall or damage DNA replication forks are widely used for chemotherapy, in the attempt to selectively target highly proliferating cancer cells. Our work provides a new rationale to design novel molecularly-guided treatments targeting the pathways of replication stress response to cancer chemotherapeutics.
Recent Publications
  • Combining electron microscopy with single molecule DNA fiber approaches to study DNA replication dynamics.
    Vindigni A, Lopes M. Biophys Chem. (2016) Dec 3 [Epub ahead of print].
  • The architectural chromatin factor high mobility group A1 enhances DNA ligase IV activity influencing DNA repair.
    Pellarin I, Arnoldo L, Costantini S, Pegoraro S, Ros G, Penzo C, Triolo G, Demarchi F, Sgarra R, Vindigni A, Manfioletti G. PLoS One. (2016) 11(10):e0614258.
  • Topoisomerase IIΒ mediates the resistance of glioblastoma stem cells to replication stress-inducing drugs.
    Kenig S, Faoro V, Bourkoula E, Podergajs N, Ius T, Vindigni M, Skrap M, Lah T, Cesselli D, Storici P, Vindigni A. Cancer Cell Int. (2016) J16:58.
  • Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors.
    Yamamoto K, Wang J, Sprinzen L, Xu J, Haddock CJ, Li C, Lee BJ, Loredan DG, Jiang W, Vindigni A, Wang D, Rabadan R, Zha S. Elife. (2016) 5:e14709.
  • Structural and biochemical characterization of an RNA/DNA binding motif in the N-terminal domain of RecQ4 helicases.
    Marino F, Mojumdar A, Zucchelli C, Bhardwaj A, Buratti E, Vindigni A, Musco G, Onesti S. Sci Rep. (2016) 6:21501.
  • Replication stress: getting back on track.
    Berti M, Vindigni A. Nat Struct Mol Biol. (2016) 23:103-109.

Full list of publications in PubMed: Vindigni A
Significant Publications as an Independent Investigator

Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition.

Matteo Berti, Arnab Ray Chaudhuri, Saravanabhavan Thangavel, Shivasankari Gomathinayagam, Sasa Kenig, Marko Vujanovic, Federico Odreman, Timo Glatter, Simona Graziano, Ramiro Mendoza-Maldonado, Francesca Marino, Bojana Lucic, Valentina Biasin, Matthias Gstaiger, Ruedi Aebersold, Julia M Sidorova, Raymond J. Monnat Jr., Massimo Lopes, and Alessandro Vindigni.

Nat. Struct. Mol. Biol. 20(3):347-354, 2013. (PMID 23396353).

Replication fork reversal is rapidly emerging as a pivotal mechanism of replication stress response to cancer chemotherapeutics. This work identifies the first molecular mechanism required to restart replication forks that have reversed upon treatment with DNA topoisomerase I inhibitors. It also provides a new rationale to improve current chemotherapeutic modalities based on the use of DNA replication inhibitors. This article was rated as a "must read" by the Faculty of 1000.

PARP PARylation activity is not required to form reversed forks, but it promotes the accumulation of regressed forks by inhibiting RECQ1 fork restoration activity, thus preventing premature restart of regressed forks.

DNA2 drives processing and restart of reversed replication forks in human cells.

Saravanabhavan Thangavel, Matteo Berti, Maryna Levikova, Cosimo Pinto, Shivasankari Gomathinayagam, Marko Vujanovic, Ralph Zellweger, Hayley Moore, Eu Han Lee, Eric A. Hendrickson, Petr Cejka, Sheila Stewart, Massimo Lopes, and Alessandro Vindigni.

J. Cell Biol. 208(5):545-562, 2015 (PMID 25733713).

This work defines new important roles for different human nucleases in replication stress response to cancer chemotherapeutics and opens new avenues to study the link between nucleolytic processing of stalled replication intermediates and chemotherapeutic sensitivity.

Electron micrograph of a partially single-stranded (left) and entirely double-stranded (right) reversed fork observed on genomic DNA upon HU-treatment. The black arrow points to the ssDNA region on the reversed arm.
D, daughter strand; P, parental strand; R, reversed arm.

Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration: insights from DNA complex structures.

Ashley C.W. Pike, Shivasankari Gomathinayagam, Paolo Swuec, Matteo Berti, Ying Zhang, Christina Schnecke, Francesca Marino, Frank von Delft, Ludovic Renault, Alessandro Costa, Opher Gileadi, and Alessandro Vindigni.

Proc. Natl. Acad. Sci. USA. 112(14):4286-4291, 2015. (25831490).

This work determines the first DNA complex structures of the human RECQ1 helicase. These structures provide new insight into the RecQ helicase mechanism of DNA tracking, strand separation, and Holliday junction branch migration. This work helps clarify how different RecQ enzymes are uniquely adapted to process potentially recombinogenic DNA structures that arise upon replication stress.

Overall structure of the RECQ1/DNA complex and trajectory of the ssDNA tail. Perpendicular view of isolated monomer/DNA showing the trajectory of DNA. The top and bottom strands of the tailed duplex are colored black and orange, respectively. A third ssDNA strand from an adjacent complex in the crystal, which base-pairs at the separation junction, is colored cyan.