A5072202843- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- DNA and Nucleic Acid Chemistry
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- RNA modifications and cancer
- Carcinogens and Genotoxicity Assessment
- Complement system in diseases
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
- interferon and immune responses
- Genetics and Neurodevelopmental Disorders
- Enzyme Structure and Function
- Chromatin Remodeling and Cancer
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Plant Genetic and Mutation Studies
- Epigenetics and DNA Methylation
- Bacterial Genetics and Biotechnology
- Barrier Structure and Function Studies
- Telomeres, Telomerase, and Senescence
University of Zurich
2012-2025
University Hospital of Zurich
2013-2025
Danish Cancer Society
2012
University of Copenhagen
2012
University College London
2012
Novo Nordisk Foundation
2012
The Gurdon Institute
2004-2007
University of Cambridge
2003-2007
Wellcome Trust
2004-2007
Institut de Pharmacologie et de Biologie Structurale
2001
The bacterial pathogen Helicobacter pylori chronically infects the human gastric mucosa and is leading risk factor for development of cancer. molecular mechanisms H. -associated carcinogenesis remain ill defined. In this study, we examined possibility that directly compromises genomic integrity its host cells. We provide evidence infection introduces DNA double-strand breaks (DSBs) in primary transformed murine epithelial mesenchymal induction DSBs depends on direct contact live bacteria...
During human nucleotide excision repair, damage is recognized, two incisions are made flanking a DNA lesion, and residues replaced by repair synthesis. A set of proteins required for most lesions RPA, XPA, TFIIH, XPC–hHR23B, XPG, ERCC1–XPF, but additional components have not been excluded. The complex difficult to analyze factor which has 6-subunit core (XPB, XPD, p44, p34, p52, p62) 3-subunit kinase (CAK). TFIIH roles both in basal transcription initiation several inherited disorders...
The MRE11–RAD50–Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex accumulates at sites of DNA double-strand breaks (DSBs) in microscopically discernible nuclear foci. Focus formation by the MRN is dependent on MDC1, a large protein that directly interacts with phosphorylated H2AX. In this study, we identified region MDC1 essential for focal accumulation damage. This contains multiple conserved acidic sequence motifs are constitutively vivo. We show these efficiently caseine kinase 2 (CK2)...
In response to ionizing radiation (IR), cells delay cell cycle progression and activate DNA repair. Both processes are vital for genome integrity, but the mechanisms involved in their coordination not fully understood. a mass spectrometry screen, we identified adenosine triphosphate-dependent chromatin-remodeling protein CHD4 (chromodomain helicase DNA-binding 4) as factor that becomes transiently immobilized on chromatin after IR. Knockdown of triggers enhanced Cdc25A degradation p21(Cip1)...
Among the different base excision repair pathways known, long patch of apurinic/apyrimidinic sites is an important mechanism that requires proliferating cell nuclear antigen. We have reconstituted this pathway using purified human proteins. Our data indicated efficient dependent on six components including AP endonuclease, replication factor C, antigen, DNA polymerases δ or ε, flap endonuclease 1, and ligase I. Fine mapping nucleotide replacement events showed patches extended up to a...
// Eleftherios P. Samartzis 1 , Katrin Gutsche Konstantin J. Dedes Daniel Fink Manuel Stucki and Patrick Imesch Department of Gynecology, University Hospital Zurich, Zürich, Switzerland Correspondence: Imesch, email: Keywords : ARID1A; BAF250a; SWI/SNF; PI3K/AKT pathway; AKT phosphorylation; PIK3CA; apoptosis; AKT-inhibitor; MK-2206; perifosine; PI3K-inhibitor; buparlisib (BKM120); ovarian clear cell carcinomas; endometriosis associated endometrial cancer; breast cancer Received March...
In mitosis, cells inactivate DNA double-strand break (DSB) repair pathways to preserve genome stability. However, some early signaling events still occur, such as recruitment of the scaffold protein MDC1 phosphorylated histone H2AX at DSBs. Yet, it remains unclear whether these are important for maintaining stability during mitosis. Here, we identify a highly conserved protein-interaction surface in that is by CK2 and recognized DNA-damage response mediator TOPBP1. Disruption MDC1-TOPBP1...
Abstract Induction of DNA double-strand breaks (DSBs) in ribosomal (rDNA) repeats is associated with ATM-dependent repression RNA synthesis and large-scale reorganization nucleolar architecture, but the signaling events that regulate these responses are largely elusive. Here we show response to rDNA dependent on both ATM ATR activity. We further demonstrate ATM- NBS1-dependent recruitment TOPBP1 nucleoli required for inhibition segregation breaks. Mechanistically, mediated by...
Abstract The accurate repair of DNA double-strand breaks (DSBs), highly toxic lesions, is crucial for genome integrity and tightly regulated during the cell cycle. In mitosis, cells inactivate DSB in favor a tethering mechanism that stabilizes broken chromosomes until they are repaired subsequent cycle phases. How this achieved mechanistically not yet understood, but adaptor protein TOPBP1 critically implicated process. Here, we identify CIP2A as TOPBP1-interacting regulates localization...
Aim of the study To evaluate frequency MRE11/RAD50/NBS1 (MRN)-complex loss protein expression in endometrial cancers (EC) and to determine whether MRE11 renders cancer cells sensitive Poly(ADP-ribose) polymerase (PARP)-inhibitory treatment. Methods MRN was examined 521 samples carcinomas 10 cell lines. A putative mutation hotspot form an intronic poly(T) allele sequenced selected cases (n = 26). Sensitivity PARP-inhibitor, BMN673 tested colony formation assays before after silencing using...