A5034589297- DNA Repair Mechanisms
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Genetics, Bioinformatics, and Biomedical Research
- Machine Learning in Materials Science
- RNA Interference and Gene Delivery
- Cancer-related Molecular Pathways
- Carcinogens and Genotoxicity Assessment
- PARP inhibition in cancer therapy
- Machine Learning in Bioinformatics
- Theoretical and Computational Physics
- RNA Research and Splicing
- RNA modifications and cancer
- Enzyme Structure and Function
CEA Paris-Saclay
2021-2024
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2021-2024
Centre National de la Recherche Scientifique
2021-2024
Université Paris-Saclay
2021-2024
Institut de Biologie Intégrative de la Cellule
2021-2024
Université Paris-Sud
2023
The revolution brought about by AlphaFold2 opens promising perspectives to unravel the complexity of protein-protein interaction networks. analysis networks obtained from proteomics experiments does not systematically provide delimitations regions. This is particular concern in case interactions mediated intrinsically disordered regions, which site generally small. Using a dataset protein-peptide complexes involving regions that are non-redundant with structures used training, we show when...
DNA double-strand break (DSB) repair is initiated by end resection. CtIP acts in short-range resection to stimulate MRE11–RAD50–NBS1 (MRN) endonucleolytically cleave 5′-terminated bypass protein blocks. also promotes the DNA2 helicase–nuclease accelerate long-range downstream from MRN. Here, using AlphaFold2, we identified CtIP-F728E-Y736E as a separation-of-function mutant that still proficient conjunction with MRN but not able ssDNA degradation DNA2. Accordingly, impairs physical...
Abstract The revolution brought about by AlphaFold2 and the performance of AlphaFold2-Multimer open promising perspectives to unravel complexity protein-protein interaction networks. Nevertheless, analysis networks obtained from proteomics experiments does not systematically provide delimitations regions. This is particular concern in case interactions mediated intrinsically disordered regions, which site generally small. Using a dataset protein-peptide complexes involving protein regions...
Abstract HROB promotes the MCM8-9 helicase in DNA damage response. To understand how activates MCM8-9, we defined their interaction interface. We showed that makes important yet transient contacts with both MCM8 and MCM9, binds heterodimer highest affinity. MCM8-9-HROB prefer branched structures, display low unwinding processivity. unwinds as a hexamer assembles from dimers on presence of ATP. The involves two repeating protein-protein interfaces between alternating MCM9 subunits. One these...
Mutations in homologous recombination (HR) genes, including BRCA1 , BRCA2 and the RAD51 paralog RAD51C predispose to tumorigenesis sensitize cancers DNA-damaging agents poly(ADP ribose) polymerase inhibitors. However, ∼800 missense variants of unknown significance have been identified for alone, impairing cancer risk assessment therapeutic strategies. Here, we interrogated >50 variants, finding that mutations residues conserved with strongly predicted HR deficiency disrupted interactions...
The InterEvDock3 protein docking server exploits the constraints of evolution by multiple means to generate structural models assemblies. takes as input either several sequences or 3D structures proteins known interact. It returns a set 10 consensus candidate complexes, together with interface predictions guide further experimental validation interactively. Three key novelties were implemented in help obtain more reliable models: users can (i) template-based assemblies using close and remote...
Abstract The human MCM8-9 helicase functions in concert with HROB the context of homologous recombination, but its precise function is unknown. To gain insights into how regulates MCM8-9, we first used molecular modeling and biochemistry to define their interaction interface. We show that makes important contacts both MCM8 MCM9 subunits, which directly promotes DNA-dependent ATPase activities. MCM8-9-HROB preferentially binds unwinds branched DNA structures, single-molecule experiments...
Summary In S. cerevisiae , the Mre11-Rad50-Xrs2 (MRX)-Sae2 nuclease activity is required for resection of DNA breaks with secondary structures or protein blocks, while in humans, MRE11-RAD50-NBS1 (MRN) homologue CtIP needed to initiate end all breaks. Phosphorylated Sae2/CtIP stimulates endonuclease MRX/N. Structural insights into activation Mre11 are available only organisms lacking Sae2/CtIP, so little known how activates ensemble. Here, we uncover mechanism by Sae2 using a combination...
The human MCM8-9 helicase functions in concert with HROB the context of homologous recombination, but its precise function is unknown. To gain insights into how regulates MCM8-9, we first used molecular modeling and biochemistry to define their interaction interface. We show that makes important contacts both MCM8 MCM9 subunits, which directly promotes DNA-dependent ATPase activities. MCM8-9-HROB preferentially binds unwinds branched DNA structures, single-molecule experiments reveal a low...
Abstract The biological function of natural non-coding RNAs (ncRNA) is tightly bound to their molecular structure. Sequence analyses such as multiple sequence alignments (MSA) are the bread and butter bio-molecules functional analysis; however, analyzing structure simultaneously a difficult task. In this work, we propose CARNAGE (Clustering/Alignment RNA with Graph-network Embedding), which leverages graph neural network encoder imprint structural information into sequence-like embedding;...