Lepakshi Ranjha
University of Lugano
Homologous recombinationMolecular biologyGeneticsDNABiology
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Publications 14
#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...
#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...
#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
#1Arnaud de Muyt (Curie Institute)H-Index: 2
#2Alexandra Pyatnitskaya (Curie Institute)H-Index: 1
Last. Valérie Borde (Curie Institute)H-Index: 20
view all 15 authors...
17 CitationsSource
#1Lepakshi Ranjha (USI: University of Lugano)H-Index: 7
#2Sean Michael Howard (USI: University of Lugano)H-Index: 3
Last. Petr Cejka (USI: University of Lugano)H-Index: 28
view all 3 authors...
3 Citations
#1Lepakshi Ranjha (USI: University of Lugano)H-Index: 7
#2Sean Michael Howard (USI: University of Lugano)H-Index: 3
Last. Petr Cejka (ETH Zurich)H-Index: 28
view all 3 authors...
DNA double-strand breaks arise accidentally upon exposure of DNA to radiation and chemicals or result from faulty DNA metabolic processes. DNA breaks can also be introduced in a programmed manner, such as during the maturation of the immune system, meiosis, or cancer chemo- or radiotherapy. Cells have developed a variety of repair pathways, which are fine-tuned to the specific needs of a cell. Accordingly, vegetative cells employ mechanisms that restore the integrity of broken DNA with the highe...
41 CitationsSource
#1Angelo Taglialatela (CUMC: Columbia University Medical Center)H-Index: 3
#2Silvia Alvarez (CUMC: Columbia University Medical Center)H-Index: 1
Last. Alberto Ciccia (CUMC: Columbia University Medical Center)H-Index: 20
view all 13 authors...
Summary To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces t...
67 CitationsSource
#1Yann Duroc (UPMC: Pierre-and-Marie-Curie University)H-Index: 11
#2Rajeev Kumar (UPMC: Pierre-and-Marie-Curie University)H-Index: 1
Last. Valérie Borde (UPMC: Pierre-and-Marie-Curie University)H-Index: 20
view all 14 authors...
Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutLβ complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without...
20 CitationsSource