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Cosimo Pinto
University of Zurich
Homologous recombinationHelicaseNucleaseDNABiology
8Publications
5H-index
278Citations
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Publications 9
Newest
#1Ilaria Ceppi (USI: University of Lugano)
#2Sean Michael Howard (USI: University of Lugano)H-Index: 3
Last. Petr Cejka (USI: University of Lugano)H-Index: 28
view all 7 authors...
BLM or WRN helicases function with the DNA2 helicase-nuclease to resect DNA double-strand breaks and initiate homologous recombination. Upon DNA unwinding by BLM/WRN, RPA directs the DNA2 nuclease to degrade the 59-strand, revealing the 39 overhang needed for recombination. RPA bound to ssDNA also represents a barrier, explaining the need for the motor activity of DNA2 to displace RPA prior to resection. Using ensemble and single molecule biochemistry, we show that phosphorylated CtIP dramatical...
Source
#1Cosimo Pinto (UZH: University of Zurich)H-Index: 5
#2Roopesh Anand (USI: University of Lugano)H-Index: 6
Last. Petr Cejka (ETH Zurich)H-Index: 28
view all 3 authors...
Abstract DNA end resection initiates the largely accurate repair of DNA double-strand breaks (DSBs) by homologous recombination. Specifically, recombination requires the formation of 3′ overhangs at DSB sites, which is carried out by nucleases that specifically degrade 5′-terminated DNA. In most cases, DNA end resection is a two-step process, comprising of initial short-range followed by more processive long-range resection. In this chapter, we describe selected assays that reconstitute both the...
5 CitationsSource
#1Roopesh Anand (USI: University of Lugano)H-Index: 6
#2Cosimo Pinto (UZH: University of Zurich)H-Index: 5
Last. Petr Cejka (ETH Zurich)H-Index: 28
view all 3 authors...
Abstract Accurate repair of DNA double-strand breaks (DSBs) is carried out by homologous recombination. In order to repair DNA breaks by the recombination pathway, the 5′-terminated DNA strand at DSB sites must be first nucleolytically processed to produce 3′-overhang. The process is termed DNA end resection and involves the interplay of several nuclease complexes. DNA end resection commits DSB repair to the recombination pathway including a process termed single-strand annealing, as resected DN...
5 CitationsSource
#1Maryna Levikova (UZH: University of Zurich)H-Index: 7
#2Cosimo Pinto (UZH: University of Zurich)H-Index: 5
Last. Petr Cejka (USI: University of Lugano)H-Index: 28
view all 3 authors...
16 CitationsSource
#1Cosimo Pinto (UZH: University of Zurich)H-Index: 5
#2Kristina Kasaciunaite (Leipzig University)H-Index: 2
Last. Petr Cejka (UZH: University of Zurich)H-Index: 28
view all 4 authors...
Human DNA2 (hDNA2) contains both a helicase and a nuclease domain within the same polypeptide. The nuclease of hDNA2 is involved in a variety of DNA metabolic processes. Little is known about the role of the hDNA2 helicase. Using bulk and single-molecule approaches, we show that hDNA2 is a processive helicase capable of unwinding kilobases of dsDNA in length. The nuclease activity prevents the engagement of the helicase by competing for the same substrate, hence prominent DNA unwinding by hDNA2 ...
23 CitationsSource
#1Cosimo Pinto (UZH: University of Zurich)H-Index: 5
#2Kristina Kasaciunaite (Leipzig University)H-Index: 2
Last. Petr Cejka (UZH: University of Zurich)H-Index: 28
view all 4 authors...
Source
#1Felix E. Kemmerich (WWU: University of Münster)H-Index: 4
#2Peter Daldrop (WWU: University of Münster)H-Index: 3
Last. Ralf Seidel (WWU: University of Münster)H-Index: 37
view all 6 authors...
Replication protein A (RPA) is a single-stranded DNA binding protein, involved in most aspects of eukaryotic DNA metabolism. Here, we study the behavior of RPA on a DNA substrate that mimics a replication fork. Using magnetic tweezers we show that both yeast and human RPA can open forked DNA when sufficient external tension is applied. In contrast, at low force, RPA becomes rapidly displaced by the rehybridization of the DNA fork. This process appears to be governed by the binding or the release...
12 CitationsSource
#1Saravanabhavan Thangavel (SLU: Saint Louis University)H-Index: 4
#2Matteo Berti (SLU: Saint Louis University)H-Index: 9
Last. Alessandro Vindigni (SLU: Saint Louis University)H-Index: 19
view all 14 authors...
Accurate processing of stalled or damaged DNA replication forks is paramount to genomic integrity and recent work points to replication fork reversal and restart as a central mechanism to ensuring high-fidelity DNA replication. Here, we identify a novel DNA2- and WRN-dependent mechanism of reversed replication fork processing and restart after prolonged genotoxic stress. The human DNA2 nuclease and WRN ATPase activities functionally interact to degrade reversed replication forks with a 5′-to-3′ ...
134 CitationsSource
#1Andreas Sturzenegger (UZH: University of Zurich)H-Index: 5
#2Kamila Burdova (CAS: Academy of Sciences of the Czech Republic)H-Index: 9
Last. Pavel Janscak (CAS: Academy of Sciences of the Czech Republic)H-Index: 29
view all 7 authors...
Abstract The 5′-3′ resection of DNA ends is a prerequisite for the repair of DNA double strand breaks by homologous recombination, microhomology-mediated end joining, and single strand annealing. Recent studies in yeast have shown that, following initial DNA end processing by the Mre11-Rad50-Xrs2 complex and Sae2, the extension of resection tracts is mediated either by exonuclease 1 or by combined activities of the RecQ family DNA helicase Sgs1 and the helicase/endonuclease Dna2. Although human ...
83 CitationsSource
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