RGD Reference Report - Carcinogenic heavy metals replace Ca2+ for DNA binding and annealing activities of mono-ubiquitinated annexin A1 homodimer. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Carcinogenic heavy metals replace Ca2+ for DNA binding and annealing activities of mono-ubiquitinated annexin A1 homodimer.

Authors: Hirata, A  Corcoran, GB  Hirata, F 
Citation: Hirata A, etal., Toxicol Appl Pharmacol. 2010 Oct 1;248(1):45-51. doi: 10.1016/j.taap.2010.07.005. Epub 2010 Jul 22.
RGD ID: 7421590
Pubmed: PMID:20655937   (View Abstract at PubMed)
DOI: DOI:10.1016/j.taap.2010.07.005   (Journal Full-text)

Mono-ubiquitinated annexin A1 was purified from rat liver nuclei. The homodimer form of mono-ubiquitinated annexin A1 was able to unwind dsDNA in a Mg(2+)- and ATP-dependent manner, and to anneal ssDNA in a Ca(2+)-dependent manner. Phospholipids decreased the concentration of Ca(2+) required for maximal annealing activity. Heavy metals such as As(3+), Cr(6+), Pb(2+) and Cd(2+) substituted for Ca(2+) in the ssDNA binding and annealing activities of annexin A1. While these metals inhibited the unwinding of dsDNA by nuclear annexin A1 in the presence of Mg(2+) and ATP, they enhanced dsDNA-dependent ATPase activity of annexin A1. Heavy metals may have produced dsDNA, a substrate for the DNA unwinding reaction, via the DNA annealing reaction. DNA synthesomes were isolated from L5178Y tk(+/-) mouse lymphoma cells in exponential growth, and were found to contain helicase activities. The As(3+)- or Cr(6+)-induced increases in ssDNA binding activity of DNA synthesomes were reduced by a mono-specific anti-annexin A1 antibody, but not by anti-Ig antibody. Anti-annexin A1 antibody also blocked the inhibitory and stimulatory effects of As(3+) or Cr(6+) towards DNA unwinding and annealing activities of DNA synthesomes. Based on these observations, it can be concluded that the effects of heavy metals on DNA annealing and unwinding activities are mediated, at least in substantial part, through actions of the mono-ubiquitinated annexin A1 homodimer.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
DNA duplex unwinding  IDA 7421590 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
DNA/DNA annealing activity  IDA 7421590 RGD 
double-stranded DNA helicase activity  IDA 7421590 RGD 
identical protein binding  IPIAnxa1 (Rattus norvegicus)7421590homodimerizationRGD 
single-stranded DNA binding  IDA 7421590 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Anxa1  (annexin A1)


Additional Information