Università della Svizzera italiana

Main steps in DNA double-strand break repair : An introduction to homologous recombination and related processes

Ranjha, Lepakshi ; Howard, Sean Michael ; Cejka, Petr

In: Chromosoma, 2018, vol. 127, no. 2 (June), p. 187–214

DNA double-strand breaks arise accidentally upon exposure of DNA to radiation, 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....

Università della Svizzera italiana

A meiotic XPF-ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation

De Muyt, Arnaud ; Pyatnitskaya, Alexandra ; Andréani, Jessica ; Ranjha, Lepakshi ; Laureau, Raphaëlle ; Fernandez-Vega, Ambra ; Holoch, Daniel ; Girard, Elodie ; Govin, Jérome ; Margueron, Raphaël ; Couté, Yohann ; Cejka, Petr ; Guérois, Raphaël ; Borde, Valérie

In: Genes and development, 2018, vol. 32, no. 3-4, p. 283-296

Meiotic crossover formation requires the stabilization of early recombination intermediates by a set of proteins and occurs within the environment of the chromosome axis, a structure important for the regulation of meiotic recombination events. The molecular mechanisms underlying and connecting crossover recombination and axis localization are elusive. Here, we identified the ZZS...

Università della Svizzera italiana

NBS1 promotes the endonuclease of the MRE11-RAD50 complex by sensing CtIP phosphorylation

Anand, Roopesh ; Jasrotia, Arti ; Bundschuh, Diana ; Howard, Sean Michael ; Ranjha, Lepakshi ; Stucki, Manuel ; Cejka, Petr

In: The EMBO Journal, 2019, vol. 38, no. 7, p. e101005

DNA end resection initiates DNA break repair by homologous recombination. MRE11-RAD50-NBS1 and phosphorylated CtIP perform the first resection step by MRE11-catalyzed endonucleolytic DNA cleavage. Human NBS1, more than its Xrs2 homologue from Saccharomyces cerevisiae, is crucial for this process, highlighting complex mechanisms that regulate the MRE11 nuclease in high eukaryotes. Using a...

Università della Svizzera italiana

Restoration of replication fork stability in BRCA1- and BRCA2-deficient cells by inactivation of SNF2-family fork remodelers

Taglialatela, Angelo ; Alvarez, Silvia ; Leuzzi, Giuseppe ; Sannino, Vincenzo ; Ranjha, Lepakshi ; Huang, Jen-Wei ; Madubata, Chioma ; Anand, Roopesh ; Levy, Brynn ; Rabadan, Raul ; Cejka, Petr ; Costanzo, Vincenzo ; Ciccia, Alberto

In: Molecular Cell, 2017, vol. 68, no. 2, p. 414-430.e8

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...

Università della Svizzera italiana

Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2

Ranjha, Lepakshi ; Levikova, Maryna ; Altmannova, Veronika ; Krejci, Lumir ; Cejka, Petr

In: Communications Biology, 2019, vol. 2, p. 174

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...