Fabio Vanoli
Memorial Sloan Kettering Cancer Center
DNA repairDNA damageMolecular biologyGeneticsBiology
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Publications 20
#1Rohit Prakash (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
#2thomas sandoval (MSK: Memorial Sloan Kettering Cancer Center)
Last. Kara A. Bernstein (University of Pittsburgh)H-Index: 18
view all 15 authors...
Homology-directed repair (HDR), a critical DNA repair pathway in mammalian cells, is complex, leading to multiple outcomes with different impacts on genomic integrity. However, the factors that control these different outcomes are often not well understood. Here we show that SWS1-SWSAP1-SPIDR controls distinct types of HDR. Despite their requirement for stable assembly of RAD51 recombinase at DNA damage sites, these proteins are not essential for intra-chromosomal HDR, providing insight into why...
#1Fabio Vanoli (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 13
#2Maria Jasin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
Abstract Recurrent chromosomal translocations often lead to expression of fusion proteins associated with oncogenic transformation. To study translocations and downstream events, genome editing techniques have been developed to generate chromosomal translocations through non-homologous end joining of DNA double-strand breaks introduced at the two participating endogenous loci. However, the frequencies at which these events occur is usually too low to efficiently clone cells carrying the transloc...
5 CitationsSource
#1Fabio Vanoli (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 13
#2Mark J. Tomishima (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 21
Last. Maria Jasin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
view all 7 authors...
Gene editing techniques have been extensively used to attempt to model recurrent genomic rearrangements found in tumor cells. These methods involve the induction of double-strand breaks at endogenous loci followed by the identification of breakpoint junctions within a population, which typically arise by nonhomologous end joining. The low frequency of these events, however, has hindered the cloning of cells with the desired rearrangement before oncogenic transformation. Here we present a strateg...
14 CitationsSource
#1Fabio Vanoli (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 13
#2Shuhei Ito (Kyushu University)
Last. Maria Jasin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
view all 6 authors...
Poly(ADP-ribose) polymerases (PARPs) are the first proteins involved in cellular DNA damage response pathways to be targeted by specific inhibitors for clinical benefit. Tumors with defects in homologous recombination (HR) are hypersensitive to PARP inhibitors (PARPi), and early phase clinical trials have been promising in patients with advanced BRCA1 and BRCA2-associated breast, ovary and prostate cancer. Unlike HR-defective cells, HR-proficient cells manifest low cytotoxicity when exposed to P...
#1Cynthia L. Browning (UMaine: University of Maine)H-Index: 1
#2Qin Qin (VT: Virginia Tech)H-Index: 1
Last. John Pierce Wise (UMaine: University of Maine)H-Index: 1
view all 7 authors...
Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen...
12 CitationsSource
#1Lianne E.M. Vriend (UvA: University of Amsterdam)H-Index: 8
#2Rohit Prakash (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
Last. Przemek M. Krawczyk (UvA: University of Amsterdam)H-Index: 15
view all 8 authors...
DNA double-strand breaks (DSBs) are known to be powerful inducers of homologous recombination (HR), but single-strand breaks (nicks) have also been shown to trigger HR. Both DSB- and nick-induced HR ((nick)HR) are exploited in advanced genome-engineering approaches based on the bacterial RNA-guided nuclease Cas9. However, the mechanisms of (nick)HR are largely unexplored. Here, we applied Cas9 nickases to study (nick)HR in mammalian cells. We find that (nick)HR is unaffected by inhibition of maj...
29 CitationsSource
#1Johnathan Watkins ('KCL': King's College London)H-Index: 13
#2Daniel Weekes ('KCL': King's College London)H-Index: 9
Last. Andrew Tutt (ICR: Institute of Cancer Research)H-Index: 53
view all 22 authors...
Triple-negative breast cancers (TNBC) are characterized by a wide spectrum of genomic alterations, some of which might be caused by defects in DNA repair processes such as homologous recombination ...
48 CitationsSource
#1Marco FumasoniH-Index: 5
#2Katharina Zwicky (UZH: University of Zurich)H-Index: 4
Last. Dana BranzeiH-Index: 26
view all 5 authors...
Chromosomal replication is entwined with DNA damage tolerance (DDT) and chromatin structure establishment via elusive mechanisms. Here we examined how specific replication conditions affecting replisome architecture and repriming impact on DDT. We show that Saccharomyces cerevisiae Polα/Primase/Ctf4 mutants, proficient in bulk DNA replication, are defective in recombination-mediated damage-bypass by template switching (TS) and have reduced sister chromatid cohesion. The decrease in error-free DD...
61 CitationsSource
#1Yu Zhang (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
#2Fabio Vanoli (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 13
Last. Maria Jasin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
view all 5 authors...
Gene targeting – homologous recombination between transfected DNA and a chromosomal locus – is greatly stimulated by a DNA break in the target locus. Recently, the RNA-guided Cas9 endonuclease, involved in bacterial adaptive immunity, has been modified to function in mammalian cells. Unlike other site-specific endonucleases whose specificity resides within a protein, the specificity of Cas9-mediated DNA cleavage is determined by a guide RNA (gRNA) containing an ~20 nucleotide locus-specific RNA ...
25 CitationsSource
#1Georgios I. Karras (MPG: Max Planck Society)H-Index: 3
#2Marco Fumasoni (University of Milan)H-Index: 5
Last. Stefan Jentsch (MPG: Max Planck Society)H-Index: 61
view all 6 authors...
Summary Damaged DNA is an obstacle during DNA replication and a cause of genome instability and cancer. To bypass this problem, eukaryotes activate DNA damage tolerance (DDT) pathways that involve ubiquitylation of the DNA polymerase clamp proliferating cell nuclear antigen (PCNA). Monoubiquitylation of PCNA mediates an error-prone pathway by recruiting translesion polymerases, whereas polyubiquitylation activates an error-free pathway that utilizes undamaged sister chromatids as templates. The ...
60 CitationsSource