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Bio
I have 64 publications and I am recognized as a world-renowned expert in the field of the DNA damage response and DNA repair in vertebrate organisms.
My groundbreaking discoveries include the setup of the first a vertebrate cell-free system based on Xenopus laevis eggs extracts that recapitulates all the aspects of the DNA damage response, including the DNA damage checkpoint and the activation of DNA repair.
Using this system, I identified novel DNA damage checkpoints that prevent initiation of DNA replication following DNA damage. I showed for the first time that ATM binds to DNA containing double strand breaks and that RPA is required for ATR activation in vivo (Costanzo et al Mol Cell. 2000 and Costanzo V et al Mol Cell 2003).
I then identified a novel function for Mre11 that accounts for its essential role in vertebrates (Costanzo et al Mol Cell. 2001) showing that Mre11 is required to yield normal replication products in the absence of apparent DNA damage. These studies established a critical connection between DNA repair and DNA replication in vertebrate organisms.
Following the postdoctoral work, I was offered a position at the prestigious Clare Hall Laboratories, London Research Institute as a tenure-track group leader where I established the Genome Stability Laboratory in October 2004. There I worked side by side with Nobel Laureate Tomas Lindalh and Tim Hunt and respected colleagues. During this time, I worked on the function of the Mre11 complex and Rad51 in DNA repair and DNA replication. Here I made another seminal discovery demonstrating for the first time that Mre11 promotes degradation of nascent strands at stalled forks and that Rad51 limits this processing (Hashimoto et al Nat Struct Mol Biol. 2010). My finding about this novel function of RAD51 has contributed to start a new research field, which is currently being pursued by my laboratory and by many other labs around the word working on molecular mechanisms regulating genome stability. This novel RAD51 function has indeed been found to be critical to prevent genome instability and occurrence of chemo-resistance in cancer cells.
At Clare Hall, I produced several other papers on the identification of new regulators of cell cycle such as Cep63 and Gemc1 (Nat Cell Biol 2009 and 2010) and on the role of Plk1 and ATM/ATR in promoting DNA replication fork stability.
I also demonstrated for the first time that ATM regulates the pentose phosphate pathway promoting the formation of antioxidant molecules such as NADPH and nucleotide precursors required for DNA repair (Cosentino et al EMBO J. 2011). This finding established for the first time a direct link between DNA repair and checkpoint genes defective in cancer in cellular metabolism.
Following my move to IFOM, I reconstituted for the first time the replication, the protein composition and the structure of the chromatin associated to human centromeres (Aze et al, Nat Cell Biol. 2016), showing that repetitive DNA suppresses ATR activation and visualizing for the first time centromeric DNA loops.
More recently I have established the molecular function of Brca2 protein showing that it protects nascent DNA degradation and promotes polymerase dependent fork restart (Kolinjivadi et al, Mol Cell 2017).
My work over the years has been highlighted in several News and Views and review articles and has led to significant advance in the field of DNA damage response and DNA damage checkpoint as confirmed by work from many labs that extended our initial observations to mammalian model systems.
Research Interests
Papers共 126 篇Author StatisticsCo-AuthorSimilar Experts
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Chandler E Moore,Selin E Yalcindag,Hanna Czeladko,Ramya Ravindranathan,Yodhara Wijesekara Hanthi, Juliana C Levy,Vincenzo Sannino,Detlev Schindler,Alberto Ciccia,Vincenzo Costanzo,Andrew E H Elia
Sustainability in Energy and Buildings 2022 (2023): 12-21
CELL REPORTSno. 12 (2023): 113555-113555
PHOTONICSno. 5 (2022): 294-294
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Author Statistics
#Papers: 119
#Citation: 7691
H-Index: 41
G-Index: 87
Sociability: 6
Diversity: 0
Activity: 1
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