A5042495366- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- Advanced biosensing and bioanalysis techniques
- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Carcinogens and Genotoxicity Assessment
- Genetics and Neurodevelopmental Disorders
- Advanced Electron Microscopy Techniques and Applications
- Lung Cancer Research Studies
- Cancer-related Molecular Pathways
- RNA Research and Splicing
- Nuclear Structure and Function
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Polyomavirus and related diseases
- Herpesvirus Infections and Treatments
- Advanced Mathematical Physics Problems
- Transgenic Plants and Applications
- Molecular Junctions and Nanostructures
- Microbial Fuel Cells and Bioremediation
- Aldose Reductase and Taurine
Peking University
2015-2024
Sun Yat-sen University
2023
Sixth Affiliated Hospital of Sun Yat-sen University
2023
North China Electric Power University
2020
Stanford University
2018
National Institute on Aging
2009-2017
Center for Life Sciences
2017
State Key Laboratory of Plant Genomics
2016
State Key Laboratory of Protein and Plant Gene Research
2016
National Institutes of Health
2008-2013
BLM, the helicase mutated in Bloom syndrome, associates with topoisomerase 3α, RMI1 (RecQ-mediated genome instability), and RPA, to form a complex essential for maintenance of stability. Here we report novel component BLM complex, RMI2, which interacts through two oligonucleotide-binding (OB)-fold domains similar those RPA. The resulting named RMI, differs from RPA that it lacks obvious DNA-binding activity. Nevertheless, RMI stimulates dissolution homologous recombination intermediate vitro...
Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand breaks (DSBs), which can display different types of broken ends. However, it unclear how NHEJ factors organize diverse breaks. Here, through systematic analysis the human factor interactome, we identify PAXX as direct interactor Ku. The crystal structure similar those XRCC4 and XLF. Importantly, PAXX-deficient cells are sensitive DSB-causing agents. Moreover, epistasis demonstrates that functions together with...
Deletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents distinct PCa subtype characterized by SPOP mutation and higher instability. However, role development vivo its clinical utility remain unclear.To study management, we generated genetically engineered mouse model with prostate-specific deletion murine Chd1 as well isogenic wild-type homozygous deleted benign lines....
Abstract 53BP1 with its downstream proteins, RIF1, PTIP and REV7, antagonizes BRCA1-dependent homologous recombination (HR) promotes non-homologous end joining (NHEJ) in an unclear manner. Here we show that REV7 forms a complex two FAM35A C20ORF196. We demonstrate preferentially binds single-strand DNA (ssDNA) vitro, is recruited to DSBs as C20ORF196 of RIF1 vivo. Epistasis analysis shows both proteins act the same pathway NHEJ. The defects HR repair reduction resection broken ends...
DNA Topoisomerases are essential to resolve topological problems during metabolism in all species. However, the prevalence and function of RNA topoisomerases remain uncertain. Here, we show that topoisomerase activity is prevalent Type IA from bacteria, archaea, eukarya. Moreover, this always requires conserved core domains same catalytic residue used reaction; however, it does not absolutely require non-conserved carboxyl-terminal domain (CTD), which necessary for relaxation reactions...
The cellular pathways that restart stalled replication forks are essential for genome stability and tumor prevention. However, how many of these exist in cells selectively activated remain unclear. Here, we describe two major fork pathways, demonstrate their selection is governed by 53BP1 BRCA1, which known to control the pathway choice repair double-strand DNA breaks (DSBs). Specifically, promotes a cleavage-free pathway, whereas BRCA1 facilitates break-induced (BIR) coupled with SLX-MUS...
Eukaryotic replisomes are driven by the mini chromosome maintenance (MCM [M]) helicase complex, an offset ring locked around template for leading strand synthesis CDC45 (C) and GINS (G) proteins. Although MCM (CMG) structure implies that interstrand crosslinks (ICLs) absolute blocks to replisomes, recent studies indicate cells can restart DNA on side of ICL distal initial encounter. Here, we report requires ATR is promoted FANCD2 phosphorylated FANCM. Following introduction genomic ICLs...
Abstract The recruitment of FANCM, a conserved DNA translocase and key component several repair protein complexes, to replication forks stalled by interstrand crosslinks (ICLs) is step upstream the Fanconi anemia (FA) traverse pathways ICLs. However, detection FANCM has been technically challenging so that its mechanism remains exclusive. Here, we successfully observed at using newly developed protocol. We report depends upon intrinsic activity, DNA-binding partner FAAP24. Moreover, it...
Human cells contain five topoisomerases in the nucleus and cytoplasm, but which one is major topoisomerase for mRNAs unclear. To date, Top3β only known that possesses RNA activity, binds mRNA translation machinery interacts with an RNA-binding protein, FMRP, to promote synapse formation; gene deletion has been linked schizophrenia. Here, we show also most abundant mRNA-binding cells. Top3β, not other topoisomerases, contains a distinctive domain; of this domain diminishes amount associates...
The 53BP1-RIF1 pathway antagonizes resection of DNA broken ends and confers PARP inhibitor sensitivity on BRCA1-mutated tumors. However, it is unclear how this suppresses initiation resection. Here, we identify ASF1 as a partner RIF1 via an interacting manner similar to its interactions with histone chaperones CAF-1 HIRA. recruited distal chromatin flanking breaks by promotes non-homologous end joining (NHEJ) using chaperone activity. Epistasis analysis shows that acts in the same NHEJ RIF1,...
The MRE11-RAD50-NBS1 (MRN) complex is well known for participating in DNA damage response pathways all phases of cell cycle. Here, we show that MRN constitutes a mitosis-specific complex, named mMRN, with protein, MMAP. MMAP directly interacts MRE11 and required optimal stability the during mitosis. colocalizes mitotic spindles, MMAP-deficient cells display abnormal spindle dynamics chromosome segregation similar to MRN-deficient cells. Mechanistically, both are hyperphosphorylated by...
Abstract Topoisomerase 3β (TOP3B) and TDRD3 form a dual-activity topoisomerase complex that interacts with FMRP can change the topology of both DNA RNA. Here, we investigated post-transcriptional influence TOP3B associated proteins on mRNA translation turnover. First, discovered in human HCT116 colon cancer cells, knock-out (KO) had similar effects turnover as did TDRD3-KO, while FMRP-KO resulted rather distinct effects, indicating stronger coordination than regulation. Second, identified...