Lead effects on protamine-DNA binding

Quintanilla‐Vega, Betzabet; Hoover, Dennis J.; Bal, Wojciech; Silbergeld, Ellen K.; Waalkes, Michael P.; Anderson, Larry D.

doi:10.1002/1097-0274(200009)38:3<324::aid-ajim12>3.0.co;2-r

Cited by 53 publications

(21 citation statements)

References 45 publications

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“…It may also interfere with the ability of DNA to repair itself after genotoxic insult. By binding histones, Pb may decrease the protection these proteins give DNA, directly increasing the exposure of DNA to damaging agents [21,22]. In a study conducted by Lustberg M. et al it was found that individuals who had high levels of lead had increased cancer-caused mortality due to lung cancer and nonlung cancer [23].…”

Section: Discussionmentioning

confidence: 99%

Plasma Concentrations of Some Trace Element and Heavy Metals in Patients with Metastatic Colon Cancer

Özgür¹,

Demır²,

Doğan³

et al. 2013

JCT

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Purpose: It is well known that trace elements and heavy metals play a significant role in human health and disease. These elements play an important role in different metabolic pathways of cells and tissues. Trace element deficiency or excess is implicated in the development or progression of some cancers. We present a study which investigates serum/ plasma levels of trace-heavy elements in metastatic colon cancer patients and healthy subjects. Methods: Blood samples were collected from 29 healthy subjects and 40 patients with metastatic colon cancer in Oncology Department of Medical School of Yuzuncu Yil University. In both groups, the serum levels of copper (Cu), magnesium (Mg), lead (Pb), chromium (Cr), zinc (Zn) selenium (Se), manganese (Mn), and cadmium (Cd) were determined. Results: Higher levels of Cu, Mg, Pb, Cr, Zn, Mn and Cd were seen in patients with metastatic colon cancer compared to healthy subjects and these findings were statistically significant (p < 0.05). Se levels were noted to be lower in patients with colon cancer in comparison to healthy subjects and this finding was also statistically significant (p < 0.05). Conclusions: According to our findings there was significant diffence in trace elements and heavy metals levels between healthy subjects and metastatic colon cancer patients. Therefore heavy metal and trace elements may have prognostic significance in complex disorders including colon cancer. However, further comprehensive studies are needed in order to advance our understanding of the relationship between heavy metal and trace elements and their role in cancers.

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Section: Discussionmentioning

confidence: 99%

Plasma Concentrations of Some Trace Element and Heavy Metals in Patients with Metastatic Colon Cancer

Özgür¹,

Demır²,

Doğan³

et al. 2013

JCT

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“…6A). Cys-14 is separated from Cys-22 of the same protamine by (Arg) 7 , which corresponds to an additional one-third of a DNA helical turn (i.e. 3.5 bp) from the Cys-38 -Cys-38 disulfide bond.…”

Section: A Model For the Protamine⅐dna Complex In Bull Sperm Cellmentioning

confidence: 99%

“…DNA packaged by protamines in mature sperm cells is transcriptionally inactive and packed at a density that approaches that of a crystalline state (3,4). The packing, or condensation, of DNA by protamines has been investigated extensively by chemical and physical studies of natural sperm chromatin as well as by the investigation of protamine-DNA condensates prepared in vitro by the mixing of isolated protamines with free DNA (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). In vivo, protamines condense the DNA of vertebrate sperm cells into thousands of particles that vary in diameter from 50 to 100 nm (3, 11, 18 -21).…”

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confidence: 99%

Formation of Native-like Mammalian Sperm Cell Chromatin with Folded Bull Protamine

Vilfan

Conwell

Hud

2004

Journal of Biological Chemistry

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The DNA of most vertebrate sperm cells is packaged by protamines. The primary structure of mammalian protamine I can be divided into three domains, a central DNA binding domain that is arginine-rich and aminoand carboxyl-terminal domains that are rich in cysteine residues. In native bull sperm chromatin, intramolecular disulfide bonds hold the terminal domains of bull protamine folded back onto the central DNA binding domain, whereas intermolecular disulfide bonds between DNA-bound protamines help stabilize the chromatin of mature mammalian sperm cells. Folded bull protamine was used to condense DNA in vitro under various solution conditions. Using transmission electron microscopy and light scattering, we show that bull protamine forms particles with DNA that are morphologically similar to the subunits of native bull sperm chromatin. In addition, the stability provided by intermolecular disulfide bonds formed between bull protamine molecules within in vitro DNA condensates is comparable with that observed for native bull sperm chromatin. The importance of the bull protamine terminal domains in controlling the bull sperm chromatin morphology is indicated by our observation that DNA condensates formed under identical conditions with a fish protamine, which lacks cysteine-rich terminal domains, do not produce as uniform structures as bull protamine. A model is also presented for the bull protamine⅐DNA complex in native sperm cell chromatin that provides an explanation for the positions of the cysteine residues in bull protamine that form intermolecular disulfide bonds.During vertebrate spermiogenesis, chromatin is dramatically reorganized in developing spermatids as histones and other nonhistone-chromosomal proteins are replaced by arginine-rich oligopeptides known as protamines (1, 2). DNA packaged by protamines in mature sperm cells is transcriptionally inactive and packed at a density that approaches that of a crystalline state (3, 4). The packing, or condensation, of DNA by protamines has been investigated extensively by chemical and physical studies of natural sperm chromatin as well as by the investigation of protamine-DNA condensates prepared in vitro by the mixing of isolated protamines with free DNA (3-17). In vivo, protamines condense the DNA of vertebrate sperm cells into thousands of particles that vary in diameter from 50 to 100 nm (3, 11, 18 -21). Each protamine-DNA particle is estimated to contain on the order of 50 kb of DNA (21). Few attempts have been made to reconstitute mammalian sperm cell chromatin using purified mammalian protamines, and reported efforts have not yielded protamine-DNA condensates with DNA as highly condensed as that found in mature sperm cell chromatin (8).Some mammalian sperm cells contain two different types of protamine, referred to as protamine I and protamine II. Protamine I is present in all mammalian sperm cells, and its amino acid sequence is relatively conserved among mammals. The protamines of other vertebrates, such as fish, are similar to protamine I of mammals. P...

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“…There are recent data that lead may alter gene expression [Rossman, 2000]. One particularly intriguing mechanism for alteration of gene expression is that lead appears to interact with zinc-binding sites on human protamine, an important DNA-associated protein [Quintanilla-Vega et al, 2000]. Lead may also cause posttranslational changes in the tumor suppressor protein p53 [Quintanilla-Vega et al, 2000].…”

Section: Molecular Mechanisms Of the Carcinogenicity Of Leadmentioning

confidence: 99%

“…One particularly intriguing mechanism for alteration of gene expression is that lead appears to interact with zinc-binding sites on human protamine, an important DNA-associated protein [Quintanilla-Vega et al, 2000]. Lead may also cause posttranslational changes in the tumor suppressor protein p53 [Quintanilla-Vega et al, 2000]. Silbergeld et al [2000] concluded their analysis by stating that many of the mechanisms proposed for the carcinogenic activity of lead suggest an indirect role in carcinogenesis.…”

Section: Molecular Mechanisms Of the Carcinogenicity Of Leadmentioning

confidence: 99%