(HOME) Subject: zinc/iron
Yip R, Reeves JD, Lonnerdal B, et al., "Does Iron Supplementation
Compromise Zinc Nutrition in Healthy Infants?", (Oct 1985), The
American Journal of Clinical Nutrition, 42 (4), pp: 683-7.
Subject: zinc/DNA/iron
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J. Biol. Chem. 271: 5125-5130 (1996)[96214945]
In vivo and in vitro iron-replaced zinc finger generates free radicals and
causes DNA damage.
D. Conte, S. Narindrasorasak & B. Sarkar
Department of Biochemistry Research, The Hospital for Sick Children,
Toronto, Ontario M5G 1X8, Canada.
The estrogen receptor (ER) is a ligand-activated transcription factor
whose DNA-binding domain (ERDBD) has eight cysteines, which coordinate
two zinc atoms, forming two zinc finger-like structures. We
demonstrate the capability of iron to replace zinc in zinc finger
(hereby referred to as iron finger) both in vivo (using Escherichia
coli BL21 (DE3)) and in vitro. Iron has the ability to substitute for
zinc in the ERDBD as demonstrated by mobility shift and methylation
interference assays of iron finger, which show specific recognition of
the estrogen response element. The DNA binding constants for both in
vivo and in vitro iron-replaced zinc fingers were similar to that of
the native finger. Atomic absorption analysis revealed a ratio of 2:1
iron atoms/mol of ERDBD protein, as found for zinc in the crystal
structure of native ERDBD. More importantly, we demonstrate that iron
finger in the presence of H2O2 and ascorbate generates highly reactive
free radicals, causing a reproducible cleavage pattern to the
proximate DNA, the estrogen response element. The deoxyribose method,
used to detect free radical species generated, and the resultant
cleaved DNA ends, caused by iron finger, suggest that the free
radicals generated are hydroxyl radicals. Due to the close proximity
of the zinc finger to DNA, we postulate that iron-substituted zinc
finger may generate free radicals while bound to genetic regulatory
response elements, leading to adverse consequences such as
iron-induced toxicity and/or carcinogenesis.
MeSH Terms:
* Base Sequence
* Cloning, Molecular
* Comparative Study
* DNA Damage*
* DNA-Binding Proteins/metabolism
* DNA-Binding Proteins/biosynthesis
* DNA, Bacterial/metabolism
* DNA, Bacterial/chemistry
* Escherichia coli/metabolism
* Escherichia coli/growth & development
* Free Radicals/metabolism
* Human
* Iron/pharmacology
* Kinetics
* Methylation
* Models, Molecular
* Molecular Sequence Data
* Nucleic Acid Conformation
* Oligodeoxyribonucleotides
* Protein Structure, Secondary
* Receptors, Estrogen/metabolism
* Receptors, Estrogen/biosynthesis
* Recombinant Proteins/metabolism
* Recombinant Proteins/biosynthesis
* Support, Non-U.S. Gov't
* Time Factors
* Zinc/physiology
* Zinc Fingers*
Substances:
* Zinc
* Iron
* Recombinant Proteins
* Receptors, Estrogen
* Oligodeoxyribonucleotides
* Free Radicals
* DNA, Bacterial
* DNA-Binding Proteins
(HOME) _________________________________________________________________
Subject: Ip6/double strand break repair
Cell 2000 Sep 15;102(6):721-9
Binding of inositol phosphate to DNA-PK and stimulation of double-strand break
repair.
Hanakahi LA, Bartlet-Jones M, Chappell C, Pappin D, West SC
Imperial Cancer Research Fund, South Mimms, Hertfordshire, United
Kingdom.
In mammalian cells, double-strand breaks in DNA can be repaired by
nonhomologous end-joining (NHEJ), a process dependent upon Ku70/80,
DNA-PKcs, XRCC4, and DNA ligase IV. Starting with HeLa cell-free
extracts, which promote NHEJ in a reaction dependent upon all of these
proteins, we have purified a novel factor that stimulates DNA
end-joining in vitro. Using a combination of phosphorus NMR, mass
spectroscopy, and strong anion exchange chromatography, we identify
this factor as inositol hexakisphosphate (IP6). Purified IP6 is bound
by DNA-PK and specifically stimulates DNA-PK-dependent end-joining in
vitro. The involvement of inositol phosphate in DNA-PK-dependent NHEJ
is of particular interest since the catalytic domain of DNA-PKcs is
similar to that found in the phosphatidylinositol 3 (PI 3)-kinase
family.
PMID: 11030616, UI: 20483533
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Subject: zinc/iron
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Effects of Trace Elements Supplementation on Measures of Nutritional Status
Effects of supplementation with zinc (30.4 mg/d), copper (3.4 mg/d),
and chromium (241 ug/d) on alkaline phosphatase, serum ferritin,
hemoglobin, and plasma and erythrocyte copper, iron, and zinc were
examined in apparently healthy adults over the age of 50. Differences
were found between males and females within supplement groups. Serum
ferritin decreased significantly during and following zinc
supplementation in males. Total hemoglobin increased significantly
from baseline to four weeks post supplementation in chromium and
copper supplemented females. Alkaline phosphatase decreased from
baseline to four weeks post supplementation in all groups. The
decrease was significant in the mineral supplement groups except for
females receiving zinc--but not in the placebo group. Plasma zinc
increased significantly in zinc supplemented males and during
supplementation and in copper supplemented females from the end of
supplementation to four weeks post supplementation. In the copper
group, plasma copper decreased during supplementation in females but
was not significantly different over time in males, while in the
chromium supplemented females plasma copper increased at eight weeks
of supplementation. These results support the importance of examining
the interactive effects of minerals in both males and females.
Sponsor: Agricultural Experiment Station
PI: Andrea Arquitt
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