@article{%a1.%Y_142,

title = {Homozygous substitution of threonine 191 by proline in polymerase eta causes Xeroderma pigmentosum variant},

author = {Ricciardiello R and Forleo G and Cipolla L and van Winckel G and Marconi C and Nouspikel T and Halazonetis TD and Zgheib O and Sabbioneda S},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10784498/},

doi = {10.1038/s41598-023-51120-1},

year  = {2024},

date = {2024-02-12},

journal = {Scientific reports},

volume = {14},

issue = {1},

pages = {1117},

abstract = {DNA polymerase eta (Pol-eta) is the only translesion synthesis polymerase capable of error-free bypass of UV-induced cyclobutane pyrimidine dimers. A deficiency in Polη function is associated with the human disease Xeroderma pigmentosum variant (XPV). We hereby report the case of a 60-year-old woman known for XPV and carrying a Pol-eta Thr191Pro variant in homozygosity. We further characterize the variant in vitro and in vivo, providing molecular evidence that the substitution abrogates polymerase activity and results in UV sensitivity through deficient damage bypass. This is the first functional molecular characterization of a missense variant of Pol-eta, whose reported pathogenic variants have thus far been loss of function truncation or frameshift mutations. Our work allows the upgrading of Pol-eta Thr191Pro from 'variant of uncertain significance' to 'likely pathogenic mutant', bearing direct impact on molecular diagnosis and genetic counseling. Furthermore, we have established a robust experimental approach that will allow a precise molecular analysis of further missense mutations possibly linked to XPV. Finally, it provides insight into critical Pol-eta residues that may be targeted to develop small molecule inhibitors for cancer therapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_68,

title = {Sex specific regulation of TSPY-Like 2 in the DNA damage response of cancer cells},

author = {Cardano M and Magni M and Alfieri R and Chan SY and Sabbioneda S and Buscemi G and Zannini L},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015022/},

doi = {10.1038/s41419-023-05722-2},

year  = {2023},

date = {2023-03-01},

journal = {Cell death and disease},

volume = {14},

issue = {3},

pages = {197},

abstract = {Females have a lower probability to develop somatic cancers and a better response to chemotherapy than males. However, the reasons for these differences are still not well understood. The X-linked gene TSPY-Like 2 (TSPYL2) encodes for a putative tumor suppressor protein involved in cell cycle regulation and DNA damage response (DDR) pathways. Here, we demonstrate that in unstressed conditions TSPYL2 is maintained at low levels by MDM2-dependent ubiquitination and proteasome degradation. Upon genotoxic stress, E2F1 promotes TSPYL2 expression and protein accumulation in non-transformed cell lines. Conversely, in cancer cells, TSPYL2 accumulates only in females or in those male cancer cells that lost the Y-chromosome during the oncogenic process. Hence, we demonstrate that while TSPYL2 mRNA is induced in all the tested tumor cell lines after DNA damage, TSPYL2 protein stability is increased only in female cancer cells. Indeed, we found that TSPYL2 accumulation, in male cancer cells, is prevented by the Y-encoded protein SRY, which modulates MDM2 protein levels. In addition, we demonstrated that TSPYL2 accumulation is required to sustain cell growth arrest after DNA damage, possibly contributing to protect normal and female cancer cells from tumor progression. Accordingly, TSPYL2 has been found more frequently mutated in female-specific cancers. These findings demonstrate for the first time a sex-specific regulation of TSPYL2 in the DDR of cancer cells and confirm the existence of sexual dimorphism in DNA surveillance pathways.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_131,

title = {A Role for Human DNA Polymerase lambda in Alternative Lengthening of Telomeres},

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

url = {https://www.mdpi.com/1422-0067/22/5/2365},

doi = {10.3390/ijms22052365},

year  = {2021},

date = {2021-03-09},

journal = {International journal of molecular sciences},

volume = {22},

number = {5},

pages = {2365},

abstract = {Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol lambda) in ALT cells represses ALT activity and induces telomeric stress. In addition, replication stress in the absence of Pol lambda, strongly affects the survival of ALT cells. In vitro, Pol lambda can promote annealing of even a single G-rich telomeric repeat to its complementary strand and use it to prime DNA synthesis. The noncoding telomeric repeat containing RNA TERRA and replication protein A negatively regulate this activity, while the Protection of Telomeres protein 1 (POT1)/TPP1 heterodimer stimulates Pol lambda. Pol lambda associates with telomeres and colocalizes with TPP1 in cells. In summary, our data suggest a role of Pol lambda in the maintenance of telomeres by the ALT mechanism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__491,

title = {DROSHA is recruited to DNA damage sites by the MRN complex to promote non-homologous end-joining},

author = {Cabrini M and Roncador M and Galbiati A and Cipolla L and Maffia A and Iannelli F and Sabbioneda S and {d'Adda di Fagagna F} and Francia S},

url = {https://jcs.biologists.org/content/early/2021/02/04/jcs.249706.long},

doi = {10.1242/jcs.249706},

year  = {2021},

date = {2021-03-09},

journal = {Journal of cell science},

volume = {134},

number = {6},

pages = {jcs249706},

abstract = {The DNA damage response (DDR) is the signaling cascade that recognizes DNA double-strand breaks (DSB) and promotes their resolution via the DNA repair pathways of Non-Homologous End Joining (NHEJ) or Homologous Recombination (HR). We and others have shown that DDR activation requires DROSHA. However, whether DROSHA exerts its functions by associating with damage sites, what controls its recruitment and how DROSHA influences DNA repair, remains poorly understood. Here we show that DROSHA associates to DSBs independently from transcription. Neither H2AX, nor ATM nor DNA-PK kinase activities are required for its recruitment to break site. Rather, DROSHA interacts with RAD50 and inhibition of MRN by Mirin treatment abolishes this interaction. MRN inactivation by RAD50 knockdown or mirin treatment prevents DROSHA recruitment to DSB and, as a consequence, also 53BP1 recruitment. During DNA repair, DROSHA inactivation reduces NHEJ and boosts HR frequency. Indeed, DROSHA knockdown also increase the association of downstream HR factors such as RAD51 to DNA ends. Overall, our results demonstrate that DROSHA is recruited at DSBs by the MRN complex and direct DNA repair toward NHEJ.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Yb_70,

title = {Elongating RNA polymerase II and RNA:DNA hybrids hinder fork progression and gene expression at sites of head-on replication-transcription collisions},

author = {Zardoni L and Nardini E and Brambati A and Lucca C and Choudhary R and Loperfido F and Sabbioneda S and Liberi G},

url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkab1146/6456226},

doi = {10.1093/nar/gkab1146},

year  = {2021},

date = {2021-12-14},

urldate = {2021-12-14},

journal = {Nucleic acids research},

volume = {49},

number = {22},

pages = {12769-12784},

abstract = {Uncoordinated clashes between replication forks and transcription cause replication stress and genome instability, which are hallmarks of cancer and neurodegeneration. Here, we investigate the outcomes of head-on replication-transcription collisions, using as a model system budding yeast mutants for the helicase Sen1, the ortholog of human Senataxin. We found that RNA Polymerase II accumulates together with RNA:DNA hybrids at sites of head-on collisions. The replication fork and RNA Polymerase II are both arrested during the clash, leading to DNA damage and, in the long run, the inhibition of gene expression. The inactivation of RNA Polymerase II elongation factors, such as the HMG-like protein Spt2 and the DISF and PAF complexes, but not alterations in chromatin structure, allows replication fork progression through transcribed regions. Attenuation of RNA Polymerase II elongation rescues RNA:DNA hybrid accumulation and DNA damage sensitivity caused by the absence of Sen1, but not of RNase H proteins, suggesting that such enzymes counteract toxic RNA:DNA hybrids at different stages of the cell cycle with Sen1 mainly acting in replication. We suggest that the main obstacle to replication fork progression is the elongating RNA Polymerase II engaged in an R-loop, rather than RNA:DNA hybrids per se or hybrid-associated chromatin modifications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_457,

title = {From R-Loops to G-Quadruplexes: Emerging New Threats for the Replication Fork.},

author = {Maffia A and Ranise C and Sabbioneda S},

url = {https://www.mdpi.com/1422-0067/21/4/1506},

doi = {10.3390/ijms21041506},

year  = {2020},

date = {2020-01-01},

journal = {International journal of molecular sciences},

volume = {21},

number = {4},

pages = {e1506},

abstract = {Replicating the entire genome is one of the most complex tasks for all organisms. Research carried out in the last few years has provided us with a clearer picture on how cells preserve genomic information from the numerous insults that may endanger its stability. Different DNA repair pathways, coping with exogenous or endogenous threat, have been dissected at the molecular level. More recently, there has been an increasing interest towards intrinsic obstacles to genome replication, paving the way to a novel view on genomic stability. Indeed, in some cases, the movement of the replication fork can be hindered by the presence of stable DNA: RNA hybrids (R-loops), the folding of G-rich sequences into G-quadruplex structures (G4s) or repetitive elements present at Common Fragile Sites (CFS). Although differing in their nature and in the way they affect the replication fork, all of these obstacles are a source of replication stress. Replication stress is one of the main hallmarks of cancer and its prevention is becoming increasingly important as a target for future chemotherapeutics. Here we will try to summarize how these three obstacles are generated and how the cells handle replication stress upon their encounter. Finally, we will consider their role in cancer and their exploitation in current chemotherapeutic approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_472,

title = {Novel alternative ribonucleotide excision repair pathways in human cells by DDX3X and specialized DNA polymerases. },

author = {Riva V and Garbelli A and Casiraghi F and Arena F and Trivisani CI and Gagliardi A and Bini L and Schroeder M and Maffia A and Sabbioneda S and Maga G},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672437/},

doi = {10.1093/nar/gkaa948},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic acids research},

volume = {48},

number = {20},

pages = {11551-11565},

abstract = {Removal of ribonucleotides (rNMPs) incorporated into the genome by the ribonucleotide excision repair (RER) is essential to avoid genetic instability. In eukaryotes, the RNaseH2 is the only known enzyme able to incise 5' of the rNMP, starting the RER process, which is subsequently carried out by replicative DNA polymerases (Pols) delta or epsilon, together with Flap endonuclease 1 (Fen-1) and DNA ligase 1. Here, we show that the DEAD-box RNA helicase DDX3X has RNaseH2-like activity and can support fully reconstituted in vitro RER reactions, not only with Pol δ but also with the repair Pols beta and lambda. Silencing of DDX3X causes accumulation of rNMPs in the cellular genome. These results support the existence of alternative RER pathways conferring high flexibility to human cells in responding to the threat posed by rNMPs incorporation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%k,

title = {Cellular stress due to impairment of collagen prolyl hydroxylation complex is rescued by the chaperone 4-phenylbutyrate.},

author = {Besio R and Garibaldi N and Leoni L and Cipolla L and Sabbioneda S and Biggiogera M and Mottes M and Aglan M and Otaify GA and Temtamy SA and Rossi A and Forlino A.},

url = {https://dmm.biologists.org/content/12/6/dmm038521.long},

doi = {10.1242/dmm.038521},

year  = {2019},

date = {2019-02-15},

journal = {Disease models & mechanisms},

volume = {12},

number = {6},

abstract = {Osteogenesis imperfecta (OI) types VII, VIII and IX, caused by recessive mutations in cartilage-associated protein (CRTAP), prolyl-3-hydroxylase 1 (P3H1) and cyclophilin B (PPIB), respectively, are characterized by the synthesis of overmodified collagen. The genes encode for the components of the endoplasmic reticulum (ER) complex responsible for the 3-hydroxylation of specific proline residues in type I collagen. Our study dissects the effects of mutations in the proteins of the complex on cellular homeostasis, using primary fibroblasts from seven recessive OI patients. In all cell lines, the intracellular retention of overmodified type I collagen molecules causes ER enlargement associated with the presence of protein aggregates, activation of the PERK branch of the unfolded protein response and apoptotic death. The administration of 4-phenylbutyrate (4-PBA) alleviates cellular stress by restoring ER cisternae size, and normalizing the phosphorylated PERK (p-PERK):PERK ratio and the expression of apoptotic marker. The drug also has a stimulatory effect on autophagy. We proved that the rescue of cellular homeostasis following 4-PBA treatment is associated with its chaperone activity, since it increases protein secretion, restoring ER proteostasis and reducing PERK activation and cell survival also in the presence of pharmacological inhibition of autophagy. Our results provide a novel insight into the mechanism of 4-PBA action and demonstrate that intracellular stress in recessive OI can be alleviated by 4-PBA therapy, similarly to what we recently reported for dominant OI, thus allowing a common target for OI forms characterized by overmodified collagen.This article has an associated First Person interview with the first author of the paper. 2019. Published by The Company of Biologists Ltd.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_39,

title = {Chk1 loss creates replication barriers that compromise cell survival independently of excess origin firing.},

author = {{Gonzalez Besteiro MA} and Calzetta NL and Loureiro SM and Habif M and Betous R and Pillaire MJ and Maffia A and Sabbioneda S and Hoffmann JS and Gottifredi V},

url = {https://www.embopress.org/doi/full/10.15252/embj.2018101284},

doi = {10.15252/embj.2018101284},

year  = {2019},

date = {2019-02-24},

journal = {EMBO Journal},

volume = {38},

number = {e101284},

abstract = {The effectiveness of checkpoint kinase 1 (Chk1) inhibitors at killing cancer cells is considered to be fully dependent on their effect on DNA replication initiation. Chk1 inhibition boosts origin firing, presumably limiting the availability of nucleotides and in turn provoking the slowdown and subsequent collapse of forks, thus decreasing cell viability. Here we show that slow fork progression in Chk1‐inhibited cells is not an indirect effect of excess new origin firing. Instead, fork slowdown results from the accumulation of replication barriers, whose bypass is impeded by CDK‐dependent phosphorylation of the specialized DNA polymerase eta (Polη). Also in contrast to the linear model, the accumulation of DNA damage in Chk1‐deficient cells depends on origin density but is largely independent of fork speed. Notwithstanding this, origin dysregulation contributes only mildly to the poor proliferation rates of Chk1‐depleted cells. Moreover, elimination of replication barriers by downregulation of helicase components, but not their bypass by Polη, improves cell survival. Our results thus shed light on the molecular basis of the sensitivity of tumors to Chk1 inhibition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%j,

title = {Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells.},

author = {Belloni E and {Di Matteo A} and Pradella D and Vacca M and Wyatt CDR and Alfieri R and Maffia A and Sabbioneda S and Ghigna C},

url = {https://www.mdpi.com/2073-4409/8/12/1498},

doi = {10.3390/cells8121498},

year  = {2019},

date = {2019-11-20},

urldate = {2019-11-20},

journal = {Cells},

volume = {8},

number = {12},

pages = { pii: E1498},

abstract = {Alternative splicing (AS) plays an important role in expanding the complexity of the human genome through the production of specialized proteins regulating organ development and physiological functions, as well as contributing to several pathological conditions. How AS programs impact on the signaling pathways controlling endothelial cell (EC) functions and vascular development is largely unknown. Here we identified, through RNA-seq, changes in mRNA steady-state levels in ECs caused by the neuro-oncological ventral antigen 2 (Nova2), a key AS regulator of the vascular morphogenesis. Bioinformatics analyses identified significant enrichment for genes regulated by peroxisome proliferator-activated receptor-gamma (Ppar-γ) and E2F1 transcription factors. We also showed that Nova2 in ECs controlled the AS profiles of Ppar-γ and E2F dimerization partner 2 (Tfdp2), thus generating different protein isoforms with distinct function (Ppar-γ) or subcellular localization (Tfdp2). Collectively, our results supported a mechanism whereby Nova2 integrated splicing decisions in order to regulate Ppar-γ and E2F1 activities. Our data added a layer to the sequential series of events controlled by Nova2 in ECs to orchestrate vascular biology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%w,

title = {UBR5 interacts with the replication fork and protects DNA replication from DNA polymerase eta toxicity.},

author = {Cipolla L and Bertoletti F and Maffia A and Liang CC and Lehmann AR and Cohn MA and Sabbioneda S},

url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz824/5581729},

doi = {10.1093/nar/gkz824},

year  = {2019},

date = {2019-10-02},

journal = {Nucleic acids research},

volume = {47},

number = {21},

pages = {11268-11283},

abstract = {Accurate DNA replication is critical for the maintenance of genome integrity and cellular survival. Cancer-associated alterations often involve key players of DNA replication and of the DNA damage-signalling cascade. Post-translational modifications play a fundamental role in coordinating replication and repair and central among them is ubiquitylation. We show that the E3 ligase UBR5 interacts with components of the replication fork, including the translesion synthesis (TLS) polymerase polη. Depletion of UBR5 leads to replication problems, such as slower S-phase progression, resulting in the accumulation of single stranded DNA. The effect of UBR5 knockdown is related to a mis-regulation in the pathway that controls the ubiquitylation of histone H2A (UbiH2A) and blocking this modification is sufficient to rescue the cells from replication problems. We show that the presence of pol eta is the main cause of replication defects and cell death when UBR5 is silenced. Finally, we unveil a novel interaction between polη and H2A suggesting that UbiH2A could be involved in pol eta recruitment to the chromatin and the regulation of TLS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_113,

title = {4-PBA ameliorates cellular homeostasis in fibroblasts from osteogenesis imperfecta patients by enhancing autophagy and stimulating protein secretion.},

author = {Besio R and Iula G and Garibaldi N and Cipolla L and Sabbioneda S and Biggiogera M and Marini JC and Rossi A and Forlino A},

url = {https://www.sciencedirect.com/science/article/pii/S0925443918300450?via%3Dihub},

doi = {10.1016/j.bbadis.2018.02.002},

year  = {2018},

date = {2018-02-23},

journal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease},

volume = {1864},

pages = {1642-1652},

abstract = {"The clinical phenotype in osteogenesis imperfecta (OI) is attributed to the dominant negative function of mutant type I collagen molecules in the extracellular matrix, by altering its structure and function. Intracellular retention of mutant collagen has also been reported, but its effect on cellular homeostasis is less characterized. Using OI patient fibroblasts carrying mutations in the α1(I) and α2(I) chains we demonstrate that retained collagen molecules are responsible for endoplasmic reticulum (ER) enlargement and activation of the unfolded protein response (UPR) mainly through the eukaryotic translation initiation factor 2 alpha kinase 3 (PERK) branch. Cells carrying α1(I) mutations upregulate autophagy, while cells with α2(I) mutations only occasionally activate the autodegradative response. Despite the autophagy activation to face stress conditions, apoptosis occurs in all mutant fibroblasts. To reduce cellular stress, mutant fibroblasts were treated with the FDA-approved chemical chaperone 4-phenylbutyric acid. The drug rescues cell death by modulating UPR activation thanks to both its chaperone and histone deacetylase inhibitor abilities. As chaperone it increases general cellular protein secretion in all patients' cells as well as collagen secretion in cells with the most C-terminal mutation. As histone deacetylase inhibitor it enhances the expression of the autophagic gene Atg5 with a consequent stimulation of autophagy. These results demonstrate that the cellular response to ER stress can be a relevant target to ameliorate OI cell homeostasis.

"},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_189,

title = {Phosphorylation regulates human pol-eta stability and damage bypass throughout the cell cycle.},

author = {Bertoletti F and Cea V and Liang CC and Lanati T and Maffia A and Avarello MDM and Cipolla L and Lehmann AR and Cohn MA and Sabbioneda S},

url = {https://academic.oup.com/nar/article/45/16/9441/4002723},

doi = {10.1093/nar/gkx619},

year  = {2017},

date = {2017-09-19},

journal = {Nucleic Acids Research},

volume = {45},

number = {16},

pages = {9441-9454},

abstract = {DNA translesion synthesis (TLS) is a crucial damage tolerance pathway that oversees the completion of DNA replication in the presence of DNA damage. TLS polymerases are capable of bypassing a distorted template but they are generally considered inaccurate and they need to be tightly regulated. We have previously shown that pol-eta is phosphorylated on Serine 601 after DNA damage and we have demonstrated that this modification is important for efficient damage bypass. Here we report that pol-eta is also phosphorylated by CDK2, in the absence of damage, in a cell cycle-dependent manner and we identify serine 687 as an important residue targeted by the kinase. We discover that phosphorylation on serine 687 regulates the stability of the polymerase during the cell cycle, allowing it to accumulate in late S and G2 when productive TLS is critical for cell survival. Furthermore, we show that alongside the phosphorylation of S601, the phosphorylation of S687 and S510, S512 and/or S514 are important for damage bypass and cell survival after UV irradiation. Taken together our results provide new insights into how cells can, at different times, modulate DNA TLS for improved cell survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_190,

title = {Ribonucleotide incorporation by human DNA polymerase eta impacts translesion synthesis and RNase H2 activity.},

author = {Mentegari E and Crespan E and Bavagnoli L and Kissova M and Bertoletti F and Sabbioneda S and Imhof R and Sturla SJ and Nilforoushan A and Hubscher U and van Loon B and Maga G},

url = {https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw1275},

doi = {doi.org/10.1093/nar/gkw1275},

year  = {2017},

date = {2017-03-16},

journal = {Nucleic Acids Research},

volume = {45},

number = {5},

pages = {2600-2614},

abstract = {Ribonucleotides (rNs) incorporated in the genome by DNA polymerases (Pols) are removed by RNase H2. Cytidine and guanosine preferentially accumulate over the other rNs. Here we show that human Pol η can incorporate cytidine monophosphate (rCMP) opposite guanine, 8-oxo-7,8-dihydroguanine, 8-methyl-2'-deoxyguanosine and a cisplatin intrastrand guanine crosslink (cis-PtGG), while it cannot bypass a 3-methylcytidine or an abasic site with rNs as substrates. Pol eta is also capable of synthesizing polyribonucleotide chains, and its activity is enhanced by its auxiliary factor DNA Pol delta interacting protein 2 (PolDIP2). Human RNase H2 removes cytidine and guanosine less efficiently than the other rNs and incorporation of rCMP opposite DNA lesions further reduces the efficiency of RNase H2. Experiments with XP-V cell extracts indicate Pol eta as the major basis of rCMP incorporation opposite cis-PtGG. These results suggest that translesion synthesis by Pol eta can contribute to the accumulation of rCMP in the genome, particularly opposite modified guanines.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_287,

title = {RAD18, WRNIP1 and ATMIN promote ATM signalling in response to replication stress.},

author = {Kanu N and Zhang T and Burrell RA and Chakraborty A and Cronshaw J and Costa CD and Grönroos E and Pemberton HN and Anderton E and Gonzalez L and Sabbioneda S and Ulrich HD and Swanton C and Behrens A},

url = {http://www.nature.com/onc/journal/v35/n30/full/onc2015427a.html},

doi = {10.1038/onc.2015.427},

year  = {2016},

date = {2016-07-28},

journal = {35},

volume = {30},

number = {4009-4019},

abstract = {The DNA replication machinery invariably encounters obstacles that slow replication fork progression, and threaten to prevent complete replication and faithful segregation of sister chromatids. The resulting replication stress activates ATR, the major kinase involved in resolving impaired DNA replication. In addition, replication stress also activates the related kinase ATM, which is required to prevent mitotic segregation errors. However, the molecular mechanism of ATM activation by replication stress is not defined. Here, we show that monoubiquitinated Proliferating Cell Nuclear Antigen (PCNA), a marker of stalled replication forks, interacts with the ATM cofactor ATMIN via WRN-interacting protein 1 (WRNIP1). ATMIN, WRNIP1 and RAD18, the E3 ligase responsible for PCNA monoubiquitination, are specifically required for ATM signalling and 53BP1 focus formation induced by replication stress, not ionising radiation. Thus, WRNIP1 connects PCNA monoubiquitination with ATMIN/ATM to activate ATM signalling in response to replication stress and contribute to the maintenance of genomic stability.Oncogene advance online publication, 9 November 2015; doi:10.1038/onc.2015.427.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_262,

title = {The Regulation of DNA Damage Tolerance by Ubiquitin and Ubiquitin-Like Modifiers.},

author = {Cipolla L and Maffia A and Bertoletti F and Sabbioneda S},

url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904029/},

doi = {10.3389/fgene.2016.00105},

year  = {2016},

date = {2016-03-11},

journal = {Frontiers in Genetics},

volume = {7},

pages = {105},

abstract = {DNA replication is an extremely complex process that needs to be executed in a highly accurate manner in order to propagate the genome. This task requires the coordination of a number of enzymatic activities and it is fragile and prone to arrest after DNA damage. DNA damage tolerance provides a last line of defense that allows completion of DNA replication in the presence of an unrepaired template. One of such mechanisms is called post-replication repair (PRR) and it is used by the cells to bypass highly distorted templates caused by damaged bases. PRR is extremely important for the cellular life and performs the bypass of the damage both in an error-free and in an error-prone manner. In light of these two possible outcomes, PRR needs to be tightly controlled in order to prevent the accumulation of mutations leading ultimately to genome instability. Post-translational modifications of PRR proteins provide the framework for this regulation with ubiquitylation and SUMOylation playing a pivotal role in choosing which pathway to activate, thus controlling the different outcomes of damage bypass. The proliferating cell nuclear antigen (PCNA), the DNA clamp for replicative polymerases, plays a central role in the regulation of damage tolerance and its modification by ubiquitin, and SUMO controls both the error-free and error-prone branches of PRR. Furthermore, a significant number of polymerases are involved in the bypass of DNA damage possess domains that can bind post-translational modifications and they are themselves target for ubiquitylation. In this review, we will focus on how ubiquitin and ubiquitin-like modifications can regulate the DNA damage tolerance systems and how they control the recruitment of different proteins to the replication fork.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_286,

title = {TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.},

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

url = {http://www.nature.com/ng/journal/v48/n1/full/ng.3451.html},

doi = {doi:10.1038/ng.3451},

year  = {2016},

date = {2016-01-07},

journal = {Nature Genetics},

volume = {48},

number = {1},

pages = {36-43},

abstract = {DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_319,

title = {USP7 is essential for maintaining Rad18 stability and DNA damage tolerance.},

author = {Zlatanou A and Sabbioneda S and Miller ES and Greenwalt A and Aggathanggelou A and Maurice MM and Lehmann AR and Stankovic T and Reverdy C and Colland F and Vaziri C and Stewart GS},

url = {http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2015149a.html},

doi = {10.1038/onc.2015.149},

year  = {2016},

date = {2016-02-16},

journal = {Oncogene},

volume = {35},

number = {8},

pages = {965-976},

abstract = {965	976},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_402,

title = {Replication of Structured DNA and its implication in epigenetic stability.},

author = {Cea V and Cipolla L and Sabbioneda S},

url = {https://www.frontiersin.org/articles/10.3389/fgene.2015.00209/full},

doi = {10.3389/fgene.2015.00209},

year  = {2015},

date = {2015-03-05},

journal = {Frontiers in Genetics},

volume = {6},

pages = {209},

abstract = {DNA replication is an extremely risky process that cells have to endure in order to correctly duplicate and segregate their genome. This task is particularly sensitive to DNA damage and multiple mechanisms have evolved to protect DNA replication as a block to the replication fork could lead to genomic instability and possibly cell death. The DNA in the genome folds, for the most part, into the canonical B-form but in some instances can form complex secondary structures such as G-quadruplexes (G4). These G rich regions are thermodynamically stable and can constitute an obstacle to DNA and RNA metabolism. The human genome contains more than 350,000 sequences potentially capable to form G-quadruplexes and these structures are involved in a variety of cellular processes such as initiation of DNA replication, telomere maintenance and control of gene expression. Only recently, we started to understand how G4 DNA poses a problem to DNA replication and how its successful bypass requires the coordinated activity of ssDNA binding proteins, helicases and specialized DNA polymerases. Their role in the resolution and replication of structured DNA crucially prevents both genetic and epigenetic instability across the genome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}