Lepakshi Ranjha
University of Lugano
Publications 10
#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
view all 5 authors...
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
view all 7 authors...
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
#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
#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
#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
#1Wojciech Piwko (ETH Zurich)H-Index: 5
#2Lucie J. Mlejnkova (UZH: University of Zurich)H-Index: 2
Last.Petr Cejka (UZH: University of Zurich)H-Index: 28
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Abstract Homologous recombination (HR) is a key pathway that repairs DNA double‐strand breaks (DSBs) and helps to restart stalled or collapsed replication forks. How HR supports replication upon genotoxic stress is not understood. Using in vivo and in vitro approaches, we show that the MMS22L–TONSL heterodimer localizes to replication forks under unperturbed conditions and its recruitment is increased during replication stress in human cells. MMS22L–TONSL associates with replication protein A (R...
23 CitationsSource
#1Roopesh Anand (UZH: University of Zurich)H-Index: 6
#2Lepakshi Ranjha (UZH: University of Zurich)H-Index: 7
Last.Petr Cejka (UZH: University of Zurich)H-Index: 28
view all 4 authors...
To repair a DNA double-strand break (DSB) by homologous recombination (HR), the 5'-terminated strand of the DSB must be resected. The human MRE11-RAD50-NBS1 (MRN) and CtIP proteins were implicated in the initiation of DNA end resection, but the underlying mechanism remained undefined. Here, we show that CtIP is a co-factor of the MRE11 endonuclease activity within the MRN complex. This function is absolutely dependent on CtIP phosphorylation that includes the key cyclin-dependent kinase target m...
80 CitationsSource
#1Lepakshi Ranjha (UZH: University of Zurich)H-Index: 7
#2Roopesh Anand (UZH: University of Zurich)H-Index: 6
Last.Petr Cejka (UZH: University of Zurich)H-Index: 28
view all 3 authors...
MutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights int...
63 CitationsSource