Petr Cejka
ETH Zurich
Homologous recombinationDNA repairGeneticsDNABiology
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Publications 73
#1Wei He (UC Davis: University of California, Davis)H-Index: 1
#2H.B.D. Prasada Rao (UC Davis: University of California, Davis)H-Index: 3
Last. Harrison S. Manasca (UC Davis: University of California, Davis)H-Index: 1
view all 17 authors...
Summary Crossover recombination is essential for accurate chromosome segregation during meiosis. The MutSγ complex, Msh4-Msh5, facilitates crossing over by binding and stabilizing nascent recombination intermediates. We show that these activities are governed by regulated proteolysis. MutSγ is initially inactive for crossing over due to an N-terminal degron on Msh4 that renders it unstable by directly targeting proteasomal degradation. Activation of MutSγ requires the Dbf4-dependent kinase Cdc7 ...
1 CitationsSource
#1Elda CannavoH-Index: 13
#2Aurore SanchezH-Index: 5
Last. Jean-Baptiste CharbonnierH-Index: 23
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During prophase of the first meiotic division, cells deliberately break their DNA. These DNA breaks are repaired by homologous recombination, which facilitates proper chromosome segregation and enables reciprocal exchange of DNA segments between homologous chromosomes, thus promoting genetic diversity in the progeny. A successful completion of meiotic recombination requires nucleolytic processing of recombination intermediates. Genetic and cellular data implicated a pathway dependent on the puta...
#1Robin ÖzH-Index: 1
Last. Fredrik WesterlundH-Index: 25
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#1Aurore Sanchez (USI: University of Lugano)H-Index: 1
#1Aurore Sanchez (USI: University of Lugano)H-Index: 1
Last. Valérie Borde (Curie Institute)H-Index: 20
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Crossovers generated during the repair of programmed double-strand breaks (DSBs) are essential for fertility to allow accurate homolog segregation during the first meiotic division. Most crossovers arise through the asymmetric cleavage of double-Holliday junction (dHJ) intermediates by the MutLγ endonuclease (Mlh1-Mlh3) and an elusive non-catalytic function of Exo1, and require the Cdc5/PLK1 kinase. Here we show in budding yeast that MutLγ forms a constitutive complex with Exo1, and in meiotic c...
#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
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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...
#1Jen-Wei Huang (Columbia University)H-Index: 3
#2Angelo Taglialatela (Columbia University)H-Index: 3
Last. Alberto Ciccia (Columbia University)H-Index: 20
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Homologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. HR is carried out by a complex network of DNA repair factors. Here we identify C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a novel DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially in long-tract gene conversion, occurring downstream of RAD51 loading, consistent with a role for MCM8IP in HR-dependent DNA synthesis. Mo...
#1Kristina Kasaciunaite (Leipzig University)H-Index: 2
#2Fergus Fettes (Leipzig University)H-Index: 1
Last. Ralf Seidel (WWU: University of Münster)H-Index: 37
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1 CitationsSource
#1Lepakshi Ranjha (USI: University of Lugano)H-Index: 7
#2Maryna Levikova (UZH: University of Zurich)H-Index: 7
Last. Petr Cejka (ETH Zurich)H-Index: 28
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Dna2 is an essential nuclease-helicase that acts in several distinct DNA metabolic pathways including DNA replication and recombination. To balance these functions and prevent unscheduled DNA degradation, Dna2 activities must be regulated. Here we show that Saccharomyces cerevisiae Dna2 function is controlled by sumoylation. We map the sumoylation sites to the N-terminal regulatory domain of Dna2 and show that in vitro sumoylation of recombinant Dna2 impairs its nuclease but not helicase activit...
#1Roopesh Anand (USI: University of Lugano)H-Index: 6
#2Arti Jasrotia (UZH: University of Zurich)H-Index: 1
Last. Petr Cejka (ETH Zurich)H-Index: 28
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Abstract DNA end resection initiates DNA double‐strand break repair by homologous recombination. MRE11‐RAD50‐NBS1 and phosphorylated CtIP perform the first resection step via MRE11‐catalyzed endonucleolytic DNA cleavage. Human NBS1, more than its homologue Xrs2 in Saccharomyces cerevisiae , is crucial for this process, highlighting complex mechanisms that regulate the MRE11 nuclease in higher eukaryotes. Using a reconstituted system, we show here that NBS1, through its FHA and BRCT domains, func...
6 CitationsSource
#1Elda Cannavo (USI: University of Lugano)H-Index: 13
#2Giordano Reginato (ETH Zurich)H-Index: 1
Last. Petr Cejka (ETH Zurich)H-Index: 28
view all 3 authors...
To repair DNA double-strand breaks by homologous recombination, the 5′-terminated DNA strands must first be resected to produce 3′ overhangs. Mre11 from Saccharomyces cerevisiae is a 3′ → 5′ exonuclease that is responsible for 5′ end degradation in vivo. Using plasmid-length DNA substrates and purified recombinant proteins, we show that the combined exonuclease and endonuclease activities of recombinant MRX-Sae2 preferentially degrade the 5′-terminated DNA strand, which extends beyond the vicini...