The importance of the specific Z-DNA structure and polyamines in carcinogenesis: Fact or fiction

Juranić, Zorica D.; Kidrič, Marjetka; Tomin, R; Juranić, Ivan O.; Spužić, I; Petrović, Jelena

doi:10.1016/0306-9877(91)90284-6

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…Poly amines together with magnesium stabilize DNA structure. It has been proposed that Mg may affect oncogene amplification [42].…”

Section: Magnesium Alcohol and Cancermentioning

confidence: 99%

Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review).

Rivlin

1994

Journal of the American College of Nutrition

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A comprehensive and critical review of the evidence relating magnesium (Mg) deficiency to alcohol consumption reveals several important types of interactions. First, alcohol acts acutely as a Mg diuretic, causing a prompt, vigorous increase in the urinary excretion of this metal along with that of certain other electrolytes. Second, with chronic intake of alcohol and development of alcoholism, the body stores of Mg become depleted. During the late stages of alcoholism, the urinary excretion of Mg may become diminished as a physiological response to reduced intake and reduction of body stores. A number of aspects of the clinical syndrome of alcoholism contribute to and intensify that already existing reduction in body Mg stores. Third, a number of manifestations of alcoholism are believed due to effects of Mg deficiency, and some therapeutic benefit has been suggested from treatment of alcoholic patients with Mg. Finally, relatively little attention has been paid to the possible value of Mg administration as a preventive measure to forestall or minimize the deleterious effects of chronic use of alcohol or to prevent the development of cancer than can occur in this setting.

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“…Poly amines together with magnesium stabilize DNA structure. It has been proposed that Mg may affect oncogene amplification [42].…”

Section: Magnesium Alcohol and Cancermentioning

confidence: 99%

Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review).

Rivlin

1994

Journal of the American College of Nutrition

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“…Formation of Z-DNA has been found to stimulate homologous recombination by releasing the level of DNA supercoiling in human cells in culture (13)(14)(15)(16)(17). Z-DNA-forming CG repeats can induce small deletions in bacteria, likely generated by misalignment related to the formation of hairpin structures on individual DNA strands during either semiconservative DNA replication or refilling synthesis in the repair process (18)(19)(20)(21).…”

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confidence: 99%

Z-DNA-forming sequences generate large-scale deletions in mammalian cells

Wang

Christensen

Vásquez

2006

Proc. Natl. Acad. Sci. U.S.A.

159

194

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Spontaneous chromosomal breakages frequently occur at genomic hot spots in the absence of DNA damage and can result in translocation-related human disease. Chromosomal breakpoints are often mapped near purine-pyrimidine Z-DNA-forming sequences in human tumors. However, it is not known whether Z-DNA plays a role in the generation of these chromosomal breakages. Here, we show that Z-DNA-forming sequences induce high levels of genetic instability in both bacterial and mammalian cells. In mammalian cells, the Z-DNA-forming sequences induce double-strand breaks nearby, resulting in large-scale deletions in 95% of the mutants. These Z-DNA-induced double-strand breaks in mammalian cells are not confined to a specific sequence but rather are dispersed over a 400-bp region, consistent with chromosomal breakpoints in human diseases. This observation is in contrast to the mutations generated in Escherichia coli that are predominantly small deletions within the repeats. We found that the frequency of small deletions is increased by replication in mammalian cell extracts. Surprisingly, the large-scale deletions generated in mammalian cells are, at least in part, replication-independent and are likely initiated by repair processing cleavages surrounding the Z-DNA-forming sequence. These results reveal that mammalian cells process Z-DNA-forming sequences in a strikingly different fashion from that used by bacteria. Our data suggest that Z-DNAforming sequences may be causative factors for gene translocations found in leukemias and lymphomas and that certain cellular conditions such as active transcription may increase the risk of Z-DNA-related genetic instability.DNA repair ͉ genetic instability ͉ non-B DNA ͉ translocation

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“…Future experiments without spermine in the crystallization trials would help clarify this issue. The binding of spermine to A-, B-, and Z-DNA and its influence on the structural properties highlight the importance of polyamines in the structure and function of DNA (53)(54)(55)(56). Recent studies have shown that 1,3-propanediamine and spermidine enhance the B f A transition, while putrescine and cadaverine repress it, indicating that the trimethylene separation between polyamine charges is important in DNA structural conversion (53).…”

Section: Discussionmentioning

confidence: 99%

Interaction between the Z-Type DNA Duplex and 1,3-Propanediamine: Crystal Structure of d(CACGTG)₂ at 1.2 Å Resolution^,

et al. 2006

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The crystal structure of a hexamer duplex d(CACGTG)(2) has been determined and refined to an R-factor of 18.3% using X-ray data up to 1.2 A resolution. The sequence crystallizes as a left-handed Z-form double helix with Watson-Crick base pairing. There is one hexamer duplex, a spermine molecule, 71 water molecules, and an unexpected diamine (Z-5, 1,3-propanediamine, C(3)H(10)N(2)) in the asymmetric unit. This is the high-resolution non-disordered structure of a Z-DNA hexamer containing two AT base pairs in the interior of a duplex with no modifications such as bromination or methylation on cytosine bases. This structure does not possess multivalent cations such as cobalt hexaammine that are known to stabilize Z-DNA. The overall duplex structure and its crystal interactions are similar to those of the pure-spermine form of the d(CGCGCG)(2) structure. The spine of hydration in the minor groove is intact except in the vicinity of the T5A8 base pair. The binding of the Z-5 molecule in the minor grove of the d(CACGTG)(2) duplex appears to have a profound effect in conferring stability to a Z-DNA conformation via electrostatic complementarity and hydrogen bonding interactions. The successive base stacking geometry in d(CACGTG)(2) is similar to the corresponding steps in d(CG)(3). These results suggest that specific polyamines such as Z-5 could serve as powerful inducers of Z-type conformation in unmodified DNA sequences with AT base pairs. This structure provides a molecular basis for stabilizing AT base pairs incorporated into an alternating d(CG) sequence.

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The importance of the specific Z-DNA structure and polyamines in carcinogenesis: Fact or fiction

Cited by 4 publications

References 36 publications

Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review).

Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review).

Z-DNA-forming sequences generate large-scale deletions in mammalian cells

Interaction between the Z-Type DNA Duplex and 1,3-Propanediamine: Crystal Structure of d(CACGTG)₂ at 1.2 Å Resolution^,

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The importance of the specific Z-DNA structure and polyamines in carcinogenesis: Fact or fiction

Cited by 4 publications

References 36 publications

Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review).

Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review).

Z-DNA-forming sequences generate large-scale deletions in mammalian cells

Interaction between the Z-Type DNA Duplex and 1,3-Propanediamine: Crystal Structure of d(CACGTG)2 at 1.2 Å Resolution,

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Interaction between the Z-Type DNA Duplex and 1,3-Propanediamine: Crystal Structure of d(CACGTG)₂ at 1.2 Å Resolution^,