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Università della Svizzera italiana

Crossover or non-crossover outcomes : tailored processing of homologous recombination intermediates

Sanchez, Aurore ; Reginato, Giordano ; Cejka, Petr

In: Current opinion in genetics & development, 2021, vol. 71, p. 39-47

DNA breaks may arise accidentally in vegetative cells or in a programmed manner in meiosis. The usage of a DNA template makes homologous recombination potentially error-free, however, recombination is not always accurate. Cells possess a remarkable capacity to tailor processing of recombination intermediates to fulfill a particular need. Vegetatively growing cells aim to maintain genome...

Università della Svizzera italiana

The MRE11 complex : a versatile toolkit for the repair of broken DNA

Reginato, Giordano ; Cejka, Petr

In: DNA repair, 2020, vol. 91–92, no. July–August, p. 13 p

When DNA breaks, the ends need to be stabilized and processed to facilitate subsequent repair, which can occur by either direct but error-prone end-joining with another broken DNA molecule or a more accurate homology-directed repair by the recombination machinery. At the same time, the presence of broken DNA triggers a signaling cascade that regulates the repair events and cellular progression...

Università della Svizzera italiana

DNA (hydroxy)methylation in T helper lymphocytes

Monticelli, Silvia

In: Trends in biochemical sciences, 2019, vol. 44, no. 7, p. 589-598

Upon recognition of an antigen, the differentiation of antigen-inexperienced naïve T lymphocytes into subsets able to effectively coordinate host defense is controlled by a network of transcription factors and regulatory molecules. In the cell nucleus, these factors act in the context of epigenetic modifications that influence DNA accessibility and ultimately gene expression. This review...

Università della Svizzera italiana

Dissecting human antibody responses: useful, basic and surprising findings

Lanzavecchia, Antonio

In: EMBO molecular medicine, 2018, vol. 10, p. e8879

Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells...

Università della Svizzera italiana

SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous recombination

Daddacha, Waaqo ; Koyen, Allyson E. ; Bastien, Amanda J. ; Head,Pamela Sara E. ; Dhere, Vishal R. ; Nabeta, Geraldine N. ; Connolly, Erin C. ; Werner, Erica ; Madden, Matthew Z. ; Daly, Michele B. ; Minten, Elizabeth V. ; Whelan, Donna R. ; Schlafstein, Ashley J. ; Zhang, Hui ; Anand, Roopesh ; Doronio, Christine ; Withers, Allison E. ; Shepard, Caitlin ; Sundaram, Ranjini K. ; Deng, Xingming ; Dynan, William S. ; Wang, Ya ; Bindra, Ranjit S. ; Cejka, Petr ; Rothenberg, Eli ; Doetsch, Paul W. ; Kim, Baek ; Yu, David S.

In: Cell reports, 2017, vol. 20, no. 8, p. 1921-1935

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV- 1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate...

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...

Università della Svizzera italiana

Macrophage death following influenza vaccination initiates the inflammatory response that promotes dendritic cell function in the draining lymph node

Chatziandreou, Nikolaos ; Farsakoglu, Yagmur ; Palomino-Segura, Miguel ; D’Antuono, Rocco ; Pizzagalli, Diego Ulisse ; Sallusto, Federica ; Lukacs-Kornek, Veronika ; Uguccioni, Mariagrazia ; Corti, Davide ; Turley, Shannon J. ; Lanzavecchia, Antonio ; Carroll, Michael C. ; Gonzalez, Santiago F.

In: Cell reports, 2017, vol. 18, no. 10, p. 2427-2440

The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7)...

Università della Svizzera italiana

The Mre11-Nbs1 interface is essential for viability and tumor suppression

Kim, Jun Hyun ; Grosbart, Malgorzata ; Anand, Roopesh ; Wyman, Claire ; Cejka, Petr ; Petrini, John H.J.

In: Cell reports, 2017, vol. 18, no. 2, p. 496-507

The Mre11 complex (Mre11, Rad50, and Nbs1) is integral to both DNA repair and ataxia telangiectasia mutated (ATM)-dependent DNA damage signaling. All three Mre11 complex components are essential for viability at the cellular and organismal levels. To delineate essential and non-essential Mre11 complex functions that are mediated by Nbs1, we used TALEN-based genome editing to derive Nbs1...

Università della Svizzera italiana

Quality control mechanisms of protein biogenesis : proteostasis dies hard

Bergmann, Timothy Jan ; Brambilla Pisoni, Giorgia ; Molinari, Maurizio

In: AIMS biophysics, 2016, vol. 3, no. 4, p. 456-478

The biosynthesis of proteins entails a complex series of chemical reactions that transform the information stored in the nucleic acid sequence into a polypeptide chain that needs to properly fold and reach its functional location in or outside the cell. It is of no surprise that errors might occur that alter the polypeptide sequence leading to a non-functional proteins or that impede delivery...