Simone Sabbioneda

Istituto di Genetica Molecolare “Luigi Luca Cavalli-Sforza”
Via Abbiategrasso, 207 – 27100 PAVIA
Phone: +39 0382 546339

Curriculum Vitae – Download

Complete List of Publications – Download

Research Activity

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 catalytic 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 where polη work at the genome-wide levels and how it is regulated by a network of protein-protein interactions and post-translational modifications (Ubiquitination, phosphorylation and SUMO). 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.

Research Projects

Recent Publications


Ricciardiello R; Forleo G; Cipolla L; van Winckel G; Marconi C; Nouspikel T; Halazonetis TD; Zgheib O; Sabbioneda S

Homozygous substitution of threonine 191 by proline in polymerase eta causes Xeroderma pigmentosum variant Journal Article

In: Scientific reports, vol. 14, iss. 1, pp. 1117, 2024.

Abstract | Links | BibTeX


Cardano M; Magni M; Alfieri R; Chan SY; Sabbioneda S; Buscemi G; Zannini L

Sex specific regulation of TSPY-Like 2 in the DNA damage response of cancer cells Journal Article

In: Cell death and disease, vol. 14, iss. 3, pp. 197, 2023.

Abstract | Links | BibTeX


Mentegari E; Bertoletti F; Kissova M; Zucca E; Galli S; Tagliavini G; Garbelli A; Maffia A; Bione S; Ferrari E; d'Adda di Fagagna F; Francia S; Sabbioneda S; Chen LY; Lingner J; Bergoglio V; Hoffmann JS; Hubscher U; Crespan E; Maga G

A Role for Human DNA Polymerase lambda in Alternative Lengthening of Telomeres Journal Article

In: International journal of molecular sciences, vol. 22, no. 5, pp. 2365, 2021.

Abstract | Links | BibTeX

Cabrini M; Roncador M; Galbiati A; Cipolla L; Maffia A; Iannelli F; Sabbioneda S; d'Adda di Fagagna F; Francia S

DROSHA is recruited to DNA damage sites by the MRN complex to promote non-homologous end-joining Journal Article

In: Journal of cell science, vol. 134, no. 6, pp. jcs249706, 2021.

Abstract | Links | BibTeX

Zardoni L; Nardini E; Brambati A; Lucca C; Choudhary R; Loperfido F; Sabbioneda S; Liberi G

Elongating RNA polymerase II and RNA:DNA hybrids hinder fork progression and gene expression at sites of head-on replication-transcription collisions Journal Article

In: Nucleic acids research, vol. 49, no. 22, pp. 12769-12784, 2021.

Abstract | Links | BibTeX


Maffia A; Ranise C; Sabbioneda S

From R-Loops to G-Quadruplexes: Emerging New Threats for the Replication Fork. Journal Article

In: International journal of molecular sciences, vol. 21, no. 4, pp. e1506, 2020.

Abstract | Links | BibTeX

Riva V; Garbelli A; Casiraghi F; Arena F; Trivisani CI; Gagliardi A; Bini L; Schroeder M; Maffia A; Sabbioneda S; Maga G

Novel alternative ribonucleotide excision repair pathways in human cells by DDX3X and specialized DNA polymerases. Journal Article

In: Nucleic acids research, vol. 48, no. 20, pp. 11551-11565, 2020.

Abstract | Links | BibTeX


Besio R; Garibaldi N; Leoni L; Cipolla L; Sabbioneda S; Biggiogera M; Mottes M; Aglan M; Otaify GA; Temtamy SA; Rossi A; Forlino A.

Cellular stress due to impairment of collagen prolyl hydroxylation complex is rescued by the chaperone 4-phenylbutyrate. Journal Article

In: Disease models & mechanisms, vol. 12, no. 6, 2019.

Abstract | Links | BibTeX

Gonzalez Besteiro MA; Calzetta NL; Loureiro SM; Habif M; Betous R; Pillaire MJ; Maffia A; Sabbioneda S; Hoffmann JS; Gottifredi V

Chk1 loss creates replication barriers that compromise cell survival independently of excess origin firing. Journal Article

In: EMBO Journal, vol. 38, no. e101284, 2019.

Abstract | Links | BibTeX

Belloni E; Di Matteo A; Pradella D; Vacca M; Wyatt CDR; Alfieri R; Maffia A; Sabbioneda S; Ghigna C

Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells. Journal Article

In: Cells, vol. 8, no. 12, pp. pii: E1498, 2019.

Abstract | Links | BibTeX

Cipolla L; Bertoletti F; Maffia A; Liang CC; Lehmann AR; Cohn MA; Sabbioneda S

UBR5 interacts with the replication fork and protects DNA replication from DNA polymerase eta toxicity. Journal Article

In: Nucleic acids research, vol. 47, no. 21, pp. 11268-11283, 2019.

Abstract | Links | BibTeX


Besio R; Iula G; Garibaldi N; Cipolla L; Sabbioneda S; Biggiogera M; Marini JC; Rossi A; Forlino A

4-PBA ameliorates cellular homeostasis in fibroblasts from osteogenesis imperfecta patients by enhancing autophagy and stimulating protein secretion. Journal Article

In: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1864, pp. 1642-1652, 2018.

Abstract | Links | BibTeX


Bertoletti F; Cea V; Liang CC; Lanati T; Maffia A; Avarello MDM; Cipolla L; Lehmann AR; Cohn MA; Sabbioneda S

Phosphorylation regulates human pol-eta stability and damage bypass throughout the cell cycle. Journal Article

In: Nucleic Acids Research, vol. 45, no. 16, pp. 9441-9454, 2017.

Abstract | Links | BibTeX

Mentegari E; Crespan E; Bavagnoli L; Kissova M; Bertoletti F; Sabbioneda S; Imhof R; Sturla SJ; Nilforoushan A; Hubscher U; van Loon B; Maga G

Ribonucleotide incorporation by human DNA polymerase eta impacts translesion synthesis and RNase H2 activity. Journal Article

In: Nucleic Acids Research, vol. 45, no. 5, pp. 2600-2614, 2017.

Abstract | Links | BibTeX


Kanu N; Zhang T; Burrell RA; Chakraborty A; Cronshaw J; Costa CD; Grönroos E; Pemberton HN; Anderton E; Gonzalez L; Sabbioneda S; Ulrich HD; Swanton C; Behrens A

RAD18, WRNIP1 and ATMIN promote ATM signalling in response to replication stress. Journal Article

In: 35, vol. 30, no. 4009-4019, 2016.

Abstract | Links | BibTeX

Cipolla L; Maffia A; Bertoletti F; Sabbioneda S

The Regulation of DNA Damage Tolerance by Ubiquitin and Ubiquitin-Like Modifiers. Journal Article

In: Frontiers in Genetics, vol. 7, pp. 105, 2016.

Abstract | Links | BibTeX

Harley ME; Murina O; Leitch A; Higgs MR; Bicknell LS; Yigit G; Blackford AN; Zlatanou A; Mackenzie KJ; Reddy K; Halachev M; McGlasson S; Reijns MA; Fluteau A; Martin CA; Sabbioneda S; Elcioglu NH; Altmüller J; Thiele H; Greenhalgh L; Chessa L; Maghnie M; Salim M; Bober MB; Nürnberg P; Jackson SP; Hurles ME; Wollnik B; Stewart GS; Jackson AP

TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Journal Article

In: Nature Genetics, vol. 48, no. 1, pp. 36-43, 2016.

Abstract | Links | BibTeX

Zlatanou A; Sabbioneda S; Miller ES; Greenwalt A; Aggathanggelou A; Maurice MM; Lehmann AR; Stankovic T; Reverdy C; Colland F; Vaziri C; Stewart GS

USP7 is essential for maintaining Rad18 stability and DNA damage tolerance. Journal Article

In: Oncogene, vol. 35, no. 8, pp. 965-976, 2016.

Abstract | Links | BibTeX


Cea V; Cipolla L; Sabbioneda S

Replication of Structured DNA and its implication in epigenetic stability. Journal Article

In: Frontiers in Genetics, vol. 6, pp. 209, 2015.

Abstract | Links | BibTeX