A5009077485- DNA Repair Mechanisms
- Bacterial Genetics and Biotechnology
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Prenatal Substance Exposure Effects
- Biochemical and Molecular Research
- Metal-Catalyzed Oxygenation Mechanisms
- Cancer therapeutics and mechanisms
- ATP Synthase and ATPases Research
- Cholinesterase and Neurodegenerative Diseases
- Gut microbiota and health
- Microbial Metabolic Engineering and Bioproduction
- Proteoglycans and glycosaminoglycans research
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Complement system in diseases
- Birth, Development, and Health
- Cancer Genomics and Diagnostics
- Microbial metabolism and enzyme function
- Freezing and Crystallization Processes
- Viral gastroenteritis research and epidemiology
- Colorectal Cancer Treatments and Studies
University of Brighton
2022-2024
University of Sussex
2006-2020
Centro de Biología Molecular Severo Ochoa
2007
Universidad Autónoma de Madrid
2007
University of Birmingham
2007
European Synchrotron Radiation Facility
2007
The Royal Free Hospital
1996-1998
University College London
1996-1998
Abstract DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in presence of such impediments. In addition translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called primase–polymerase (PrimPol) that is capable directly bypassing by TLS, as well repriming downstream Here, we report PrimPol recruited reprime through its interaction with RPA....
Translesion synthesis (TLS) employs specialized DNA polymerases to bypass replication fork stalling lesions. PrimPol was recently identified as a TLS primase and polymerase involved in damage tolerance. Here, we identify novel binding partner, PolDIP2, describe how it regulates PrimPol's enzymatic activities. PolDIP2 stimulates the activity of PrimPol, enhancing both its capacity bind processivity catalytic domain. In addition, efficiency error-free 8-oxo-7,8-dihydrodeoxyguanosine (8-oxoG)...
Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess minimalist NHEJ apparatus DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure Mycobacterium tuberculosis polymerase domain LigD mediating the synapsis noncomplementary ends revealed variety interactions, including microhomology base pairing, mismatched flipped-out bases, 3'...
Significance Nonhomologous end joining (NHEJ) is a major DNA-break repair pathway in eukaryotes and prokaryotes but assumed to be absent archaea. This study establishes that functionally homologous present We have reconstituted archaeal NHEJ vitro, demonstrating it closely related the bacterial apparatus preferentially repairs breaks using RNA intermediates. identify role for unascribed nuclease preventing accumulation of genotoxic intermediates produced by strand displacement. has important...
The NHEJ (non-homologous end-joining) pathway is one of the major mechanisms for repairing DSBs (double-strand breaks) that occur in genomic DNA. In common with eukaryotic organisms, many prokaryotes possess a conserved apparatus essential repair arising stationary phase cell cycle. Although bacterial complex much more minimal than its counterpart, both pathways share number mechanistic features. relative simplicity prokaryotic makes it tractable model system investigating cellular and...
Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a 5'-tyrosyl DNA important for the repair of adducts generated by non-productive (abortive) activity topoisomerase II (TOP2). TDP2 facilitates therapeutic resistance to poisons, which are widely used in treatment range cancer types. Consequently, an interesting target development small molecule inhibitors that could restore sensitivity topoisomerase-directed therapies. Previous studies identified class deazaflavin-based molecules showed inhibitory...
Nonhomologous end-joining (NHEJ) is one of the major DNA double-strand break (DSB) repair pathways.The mechanisms by which breaks are competently brought together and extended during NHEJ poorly understood.As polymerases extend in a 5 0 -3 direction nucleotide addition to primer, it unclear how fill termini containing 3 overhangs that lack primer strand.Here, we describe, at molecular level, prokaryotic configure primer-template substrate annealing overhanging strands from opposing breaks,...
Abstract Prokaryotic Ligase D is a conserved DNA repair apparatus processing double-strand breaks in stationary phase. An orthologous C (LigC) complex also co-exists many bacterial species but its function unknown. Here we show that the LigC interacts with core BER enzymes vivo and demonstrate together these factors constitute an excision capable of repairing damaged bases abasic sites. The polymerase component, which contains C-terminal structural loop, preferentially binds to fills-in...
The non-homologous end-joining (NHEJ) pathway repairs DNA double-strand breaks (DSBs) in all domains of life. Archaea and bacteria utilize a conserved set multifunctional proteins termed Archaeo-Prokaryotic (AP) NHEJ that facilitates DSB repair. Archaeal polymerases (Pol) are capable strand displacement synthesis, whilst filling gaps or partially annealed ends, which can give rise to unligatable intermediates. However, an associated phosphoesterase (PE) resects these products ensure...
Link protein and aggrecan of the extracellular matrix each contain two proteoglycan tandem repeat (PTR) domains that interact with hyaluronate. Consensus secondary structure predictions for 59 PTR sequences 129 C‐type lectin give similar patterns a‐helices up to seven β‐strands. Protein fold recognition analyses show are highly compatible crystal structure. The predicted consists a conserved motif formed from an antiparallel β‐sheet flanked by α‐helices, being attached distinct types sheet...
Cells utilise specialized polymerases from the Primase-Polymerase (Prim-Pol) superfamily to maintain genome stability. Prim-Pol's function in maintenance pathways including replication, repair and damage tolerance. Mycobacteria contain multiple Prim-Pols required for lesion repair, Prim-PolC that performs short gap synthesis during excision repair. To understand molecular basis of Prim-PolC's recognition activities, we elucidated crystal structures pre- post-catalytic complexes bound gapped...
Studies on horseradish peroxidase C and other haem peroxidases have been carried out selected mutants in the distal cavity providing insight into functional importance of residues. Recent work has demonstrated that proximal structural features can also exert an important influence determining electronic structure pocket. To extend our understanding significance characteristics regulating properties Thr171Ser mutant constructed. Thr171 is linking residue between Ca2+ ion ligand, particular...
Aggrecan is the major proteoglycan of extracellular matrix in cartilage. It contains two N-terminal globular regions, G1 and G2, one C-terminal region, G3. G3 implicated intracellular processing aggrecan a C-type lectin carbohydrate recognition domain (CRD), frequent occurrences short complement repeat (SCR) domain, occasionally an epidermal growth factor domain. The CRD SCR domains 13 sequences were each subjected to structural analysis. Alignment 131 from all seven groups superfamily...
Abstract Background Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal spectrum disorder (FASD) and is associated with childhood growth deficiencies increased bone fracture risk. However, the effects of PAE on adult skeleton remain unclear any potential sexual dimorphism undetermined. Therefore, we utilised a murine model to examine sex differences vitro formation, juvenile skeleton. Methods Pregnant C57BL/6J female mice received 5% ethanol their drinking...
Abstract Background Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal spectrum disorder (FASD) and is associated with childhood growth deficiencies increased bone fracture risk. However, the effects of PAE on adult skeleton remain unclear any potential sexual dimorphism undetermined. Therefore, we utilised a murine model to examine sex differences vitro formation, juvenile skeleton. Methods Pregnant C57BL/6J female mice received 5% ethanol their drinking...
Conference Article| February 01 1996 Molecular modelling analyses of the C-type lectin domain in human aggrecan Nigel C. Brissett; Brissett 1Dept. Biochemistry & Biology, Royal Free Hospital School Medicine, Rowland Hill St., London NW3 2PF, U.K. Search for other works by this author on: This Site PubMed Google Scholar Stephen J. Perkins Biochem Soc Trans (1996) 24 (1): 99S. https://doi.org/10.1042/bst024099s Views Icon Article contents Figures tables Video Audio Supplementary Data Peer...