Carcinogenic heavy metals replace Ca{sup 2+} for DNA binding and annealing activities of mono-ubiquitinated annexin A1 homodimer

Journal Article · Fri Oct 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.07.005· OSTI ID:21460217

Hirata, Aiko; Corcoran, George B; Hirata, Fusao

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{sup 2+}- and ATP-dependent manner, and to anneal ssDNA in a Ca{sup 2+}-dependent manner. Phospholipids decreased the concentration of Ca{sup 2+} required for maximal annealing activity. Heavy metals such as As{sup 3+}, Cr{sup 6+}, Pb{sup 2+} and Cd{sup 2+} substituted for Ca{sup 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{sup 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{sup 3+}- or Cr{sup 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{sup 3+} or Cr{sup 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.

• OSTI ID: 21460217
• Journal Information: Toxicology and Applied Pharmacology, Vol. 248, Issue 1; Other Information: DOI: 10.1016/j.taap.2010.07.005; PII: S0041-008X(10)00231-0; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
ARSENIC IONS
CADMIUM IONS
CALCIUM IONS
CARCINOGENESIS
CARCINOGENS
CHROMIUM IONS
DNA
LEAD IONS
LYMPHOMAS
MAGNESIUM IONS
MUTAGENESIS
PHOSPHOLIPIDS
CHARGED PARTICLES
DISEASES
ESTERS
IMMUNE SYSTEM DISEASES
IONS
LIPIDS
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PATHOGENESIS