IGM-CNR, Via Abbiategrasso, 207 - 27100 Pavia, Italy

tel: +39-0382-546339
fax: +39-0382-422286 
E-mail: sabbionedaigm.cnr.it
http://www.igm.cnr.it/

Curriculum vitae

Qualifications

PhD: 2004: University of Milan, Italy (in Genetics and Molecular Sciences)

BSc: 2001: University of Milan (in Biological Sciences)

Employment and Affiliations

Researcher: Oct. 2011-date, Istituto di Genetica Molecolare, CNR

Postdoctoral Fellow: 2005-2011, Genome Damage and Stability Centre, University of Sussex, UK

Postdoctoral Fellow: 2005, Dept. of Biomolecular Sciences and Biotechnology, University of Milan

Research Activities

DNA replication is a highly processive and accurate process, but DNA damage is an extraordinary challenge and if left unrepaired can lead to increased mutagenesis, replication fork stalling and subsequent cell death. At the organism level these deficiencies can lead to cancerogenesis, neurodegeneration and immune defect. A tolerance mechanism called Post Replication Repair (PRR) can efficiently bypass unrepaired damage and allows completion of replication. PRR can bypass the damage either using translesion synthesis (TLS) polymerases or a recombination-like mechanism called “template switch”. TLS utilizes specialized DNA polymerases to replicate across damaged bases thanks to their open catalytic site that can accommodate a highly distorted template.

Most of the TLS polymerases belong to the Y family including polymerase eta, iota, kappa and Rev1 along with the  B class polymerase zeta. Due to their open ca talytic site TLS polymerases are error prone in replicating undamaged DNA and it is therefore crucial to control their recruitment during replication to avoid increased mutagenesis and genome instability. Polη has the unique capability to replicate across the major UV adduct, cyclobutane pyrimidine dimers (CPD), in an error free manner. In its absence the bypass is carried out by the other polymerases with different degrees of accuracy leading to a 40 fold increase in mutation frequency. Incorporation of the wrong nucleotides in front of the lesion it is thought to be the cause of such increased mutagenesis that could then result, in the long term, in genome instability, one of the hallmarks of cancer. A deficiency in polη is the cause of the genetic disease XPV. XPV patients present with abnormal pigmentation of the skin and are highly prone to sunlight-induced skin cancers, such as basal and squamous cell carcinomas and malignant melanomas. 

The main focus of my lab is to characterize how polη is regulated by post-translational modifications (Ubiquitination, phosphorylation and SUMO) , in the context of the cellular repair mechanisms and DNA damage checkpoints. We tackle these questions via a multidisciplinary approach ranging from cell biology to protein biochemistry in human cell lines.  Work in the lab is aimed to provide insights into the way that polη assists in the maintenance of genome stability as a barrier for cancer development, potentially providing diagnostic biomarkers for atypical XPV diagnosis and, in the long-term, hopefully contribute to the design of rational cancer therapies.

2012-2016 Marie Curie Career Integration Grant (7th framework program) – “Regulation of polη by phosphorylation, ubiquitination and SUMOylation” 

2013-2018 AIRC Start-Up Grant – “Effects on genome stability of polymerase eta regulation by the Ubiquitin and SUMO pathways”.