A5020887546- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- Plant Genetic and Mutation Studies
- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
- Cell death mechanisms and regulation
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Photosynthetic Processes and Mechanisms
University of Milano-Bicocca
2019-2024
Abstract The yeast Rif2 protein is known to inhibit Mre11 nuclease and the activation of Tel1 kinase through a short motif termed MIN, which binds Rad50 subunit simulates its ATPase activity in vitro. mechanism by restrains consequences this inhibition at DNA double-strand breaks (DSBs) are poorly understood. In study, we employed AlphaFold-Multimer modelling pinpoint validate interaction surface between MIN Rad50. We also engineered rif2-S6E mutation that enhances inhibitory effect...
Abstract DNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). NHEJ is induced the binding to DSBs of Ku70–Ku80 heterodimer, which acts as a hub for recruitment downstream components. An important issue in DSB repair maintenance ends close proximity, function that yeast involves MRX complex and Sae2. Here, we provide evidence Ku contributes keep tethered each other. The ku70-C85Y mutation, increases affinity its...
The cellular response to DNA double-strand breaks (DSBs) is initiated by the Mre11-Rad50-Xrs2 (MRX) complex that has structural and catalytic functions. MRX association at DSBs counteracted Rif2, which known interact with Rap1 binds telomeric through two tandem Myb-like domains. Whether how acts unknown. Here we show Rif2 inhibits in a manner dependent on Rap1, promotes them. turn can negatively regulate function ends also independently of Rif2. In fact, characterization mutant variants...
Homologous recombination is initiated by the nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection a two-step process. In short-range step, MRX (Mre11-Rad50-Xrs2) complex, together with Sae2, incises 5'-terminated strand at end and resects back toward end. Then, long-range nucleases Exo1 Dna2 further elongate resected tracts. We found that mutations lowering proteasome functionality bypass need for Sae2 in resection. particular, dysfunction subunit Rpn11 leads...
DNA damage elicits a checkpoint response depending on the Mec1/ATR kinase, which detects presence of single-stranded and activates effector kinase Rad53/CHK2. In Saccharomyces cerevisiae, one signaling circuits leading to Rad53 activation involves evolutionarily conserved 9-1-1 complex, acts as platform for binding Dpb11 Rad9 (referred axis) generate protein complex that allows Mec1 activation. By examining effects both loss-of-function hypermorphic mutations, here, we show Cdc55 Tpd3...