Implications of double-stranded DNA structure for development, cancer and evolution
Mitsuru Furusawa
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DOI: 10.4236/ojgen.2011.13014   PDF    HTML   XML   4,418 Downloads   10,167 Views   Citations

Abstract

Genomes consist of DNA and the genetic information is encoded in a linear form of DNA. According to the central dogma of molecular biology, the genetic information is transcribed into mRNA, and mRNA translated into a polypeptide. Gene expression should be precisely regulated in order to create progeny. Unlike RNA, DNA has double-stranded structure. Is there any specific biological reason why DNA has evolved to possess double-stranded structure? In this presentation, biological implications of the double-stranded structure of the DNA molecule will be reviewed. In eukaryotes, it has been reported that cells might have the machinery that distinguishes one DNA-strand from the other, and that the strand-recognition mechanism might control development, cancer and evolution. Three prominent models concerning biological implications of replication of double-stranded DNA will be discussed: 1) Klar’s “somatic strand-specific imprinting and selective chromatid segregation model” for differential gene regulation, 2) Cairns’ “immortal strand inheritance model” for cancer prohibition, and 3) the “disparity mutagenesis model” for the acceleration of evolution proposed by the present author.

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Furusawa, M. (2011) Implications of double-stranded DNA structure for development, cancer and evolution. Open Journal of Genetics, 1, 78-87. doi: 10.4236/ojgen.2011.13014.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Watson, J. and Crick, F. (1953) Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature, 171, 737-738. doi:10.1038/171737a0
[2] Klar. A.J. (2007) Lessons learned from studies of fission yeast mating-type switching and silencing. Annual Review of Genetics, 41, 213-236. doi:10.1146/annurev.genet.39.073103.094316
[3] Cairns, J. (1975) Mutation selection and the natural history of cancer. Nature, 255, 197-200. doi:10.1038/255197a0
[4] Furusawa, M. and Doi, H. (1992) Promotion of evolution: disparity in the frequency of strand-specific misreading between the lagging and leading strands enhances disproportionate accumulation of mutations. Journal of Theoretical Biology, 157, 127-133. doi:10.1016/S0022-5193(05)80761-1
[5] Tanabe, K., Kondo, T., Onodera, Y. and Furusawa, M. (1999) A conspicuous adaptability to antibiotics in the Escherichia coli mutator strain, dnaQ49. FEMS Microbiology Letters, 176, 191-196. doi:10.1111/j.1574-6968.1999.tb13661.x
[6] Shimoda, C., Itadani, A., Sugino, A. and Furusawa, M. (2006) Isolation of thermotolrant mutants by using proofreading-deficient DNA polymerase δ as an effective mutator in Saccharomyces serevisiae. Genes & Genetic Systems, 81, 391-397. doi:10.1266/ggs.81.391
[7] Klar, A.J. (1994) A model for specification of the left-right axis in vertebrates. Trends in Genetics, 10, 392-396. doi:10.1016/0168-9525(94)90055-8
[8] Dalgaard, J. and Klar, A.J. (2001) Does S. pombe exploit the intrinsic asymmetry of DNA synthesis to imprint daughter cells for mating-type switching? Trends in Genetics, 17, 153-157. doi:10.1016/S0168-9525(00)02203-4
[9] Dalgaard, J. and Klar, A.J. (2000) Swi 1 and swi 3 perform imprinting, pausing, and termination of DNA replication in S. pombe. Cell, 102, 745-751. doi:10.1016/S0092-8674(00)00063-5
[10] Supp, D., Witte. D., Potter. S. and Bruekner (1997) Mutation of an exonemal dynein affects left-right asymmetry in inversus viscerum mice. Nature, 389, 963-966. doi:10.1038/40140
[11] Hirokawa, N., Tanaka, Y., Okada, Y. and Takeda, S. (2006) Nodal flow and the generation of left-right asymmetry. Cell, 125, 33-45. doi:10.1016/j.cell.2006.03.002
[12] Klar, A.J. (2008) Support for the selective chromatid se- gregation hypothesis advanced for the mechanism of left- right body axis development in mice. Breast Disease, 29, 47-56.
[13] Layton, W. Jr. (1978) Heart malformations in mice homozygous for a gene causing situs inversus. Birth Defects Original Article Series, 14, 277-293.
[14] Armakolas A. and Klar, A.J. (2006) Cell type regulates selective segregation of mouse chromosome 7 DNA strands in mitosis. Science, 311, 1146-1149. doi:10.1126/science.1120519
[15] Armakolas A. and Klar, A.J. (2007) Left-light dynein motor implicated in selective chromatid segregation in mouse cells. Science, 315, 100-101. doi:10.1126/science.1129429
[16] Sandon, T., Wen, P. and LeMay, M. (1992) Reversed cerebral asymmetry in women with breast cancer. Lancet, 339, 523-524. doi:10.1016/0140-6736(92)90341-Y
[17] Klar. A.J. (2010) A hypothesis: Breast cancer predisposition and brain hemispheric laterality specification likely share a common genetic cause. Breast Disease, 31, 1-4.
[18] Klar, A.J. (2004) An epigenetic hypothesis for human brain laterality, handedness and psychosis development. Cold Sprig Harbor Symposium on Quantitative Biology, 69, 499-406.
[19] Potten. C., Hume, W., Reid, P. and Cairns, J. (1978) The segregation of DNA in epithelial stem cells. Cell, 15, 899-906. doi:10.1016/0092-8674(78)90274-X
[20] Potten, C., Owen, G. and Booth, D. (2002) Intestinal stem cells protect their genome by selective segregation of template DNA strands. Journal of Cell Science, 115, 2381-2388.
[21] Merok, J. Lansita, J., Tunstead, J. and Sherly, J. (2002) Cosegregation of chromosomes containing immortal DNA strands in cells that cycle with asymmetric stem cell kinetics. Cancer Research, 62, 66791-6795.
[22] Potten, C. (2004) Keratinocyte stem cells, label-retaining cells and possible genome protection mechanisms. Journal of Investigative Dermatology Symposium Proceedings, 9, 183-195. doi:10.1111/j.1087-0024.2004.09305.x
[23] Karpowicz, P., Morshead, C., Kam, A., Jervis, E., Ramunas, J., Cheng, V. and van der Kooy, D. (2005) Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro. Journal of Cell Biology, 170, 721-734. doi:10.1083/jcb.200502073
[24] Smith, G. (2005) Label-retaining epithelial cells in mouse mammary gland divide asymmetrically and retain their template DNA strands. Development, 132, 681-687. doi:10.1242/dev.01609
[25] Rambhatla, L., Ram-Mohan, S., Cheng, J. and Sherly, J. (2005) Immortal DNA strand cosegregation requires p53/IMPDH-dependent asymmetric self-renewal associated with adult stem cells. Cancer Research, 65, 3155- 3161.
[26] Conboy, M., Karasov, A. and Rando, T. (2007) High incidence of non-random template strand segregation and asymmetric fate determination in dividing stem cells and their progeny. PLoS Biology, 5, e102. doi:10.1371/journal.pbio.0050102
[27] Kuroki. T and Murakami, Y. (2007) Random segregation of DNA strands in epidermal basal cells. Japanese Journal of Cancer Research, 80, 637-642. doi:10.1111/j.1349-7006.1989.tb01690.x
[28] Ito, K and McGhee, J. (1987) Parental DNA strands segregate randomly during embryonic development of Caenorhabditis elegance. Cell, 49, 329-336. doi:10.1016/0092-8674(87)90285-6
[29] Ito, K., McGhee, J. and Shultz, G. (1988) Parental DNA strands segregate to both trophectoderm and inner cell mass of the developing mouse embryo. Genes & Development, 2, 929-936. doi:10.1101/gad.2.8.929
[30] Lark, K., Consigli, R. and Minocha, H. (1966) Segregation of sister chromatids in mammalian cells. Science, 154, 1202-1205. doi:10.1126/science.154.3753.1202
[31] Rosenberger, R. and Kessel, M. (1968) Nonrandom sister chromatid segregation and nuclear migration in hyphae of Asperigillus nidulans. Journal of Bacteriology, 96, 1208-1213.
[32] Wada, k., Doi, H., Tanaka, S., Wada, Y. and Furusawa, M. (1993) A neo-Darwinian algorithm: Asymmetrical mutations due to semiconservative DNA-type replication pro- mote evolution. Proceedings of the National Academy of Sciences of the United States of America, 90, 11934-11938.
[33] Eigen, M., McCaskill, J. and Schuster, P. (1989). The mo lecular quasispecies. Advance in Chemistry and Physics, 75,149-263. doi:10.1002/9780470141243.ch4
[34] Aoki, K. and Furusawa, M. (2003) Increase in error threshold for quasispecies by heterogeneous replication accuracy. Physical Review E, 68, 031904-1-031904-6.
[35] Iwaki, T., Kawamura, A., Ishino, Y., Kohno, K., Kano, Y., Goshima, N., Yara, M., Furusawa, M., Doi, H. and Imamoto. F. (1996). Preferential replication-dependent mutagenesis in the lagging DNA strand in Escherichia coli. Molecular & General Genetics, 251, 657-664.
[36] Furusawa, M. (1999) DNA’s exquisite evolutionary strategy. Kodansha Ltd., Tokyo.
[37] Albertson, T., Ogawa, M., Bugni, J., Hays, L., Chen, Y., Wang, Y., Treuting, P., Heddle, J., Goldsby, R. and Preston, B. (2009) DNA polymerase ε and δ proofreading suppress discrete mutator and cancer phenotypes in mice. Proceedings of the National Academy of Sciences of the United States of America, 106, 17101-17104. doi:10.1073/pnas.0907147106
[38] Uchimura, A., Hidaka, Y., Hirabayashi, T., Hirabayashi, M. and Yagi, T. (2009) DNA polymerase delta is required for early mammalian embryogenesis. PLoS One, 4, e4184. doi:10.1371/journal.pone.0004184
[39] Katoh, K., Kuma, K., Iwabe, N. and Miyata, T. (2005) Putative decline of DNA polymerase δ in mammalian lineage. Proceedings of the 28th Conference on The Molecular Biology Society of Japan, 7-10 December 2005, Fukuoka, 2P-0257.

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