Abstract
Mitochondrial DNAs (mtDNAs) from Chang rat solid hepatomas and Novikoff rat ascites hepatomas were examined in the electron microscope after preparation by the aqueous and by the formamide protein monolayer techniques. MtDNAs from both tumors were found to include double-forked circular molecules with a form and size suggesting they were replicative intermediates. These molecules were of two classes. In molecules of one class, all three segments were apparently totally double stranded. Molecules of the second class were distinguished by the fact that one of the segments spanning the region between the forks in which replication had occurred (the daughter segments) was either totally single stranded, or contained a single-stranded region associated with one of the forks. Daughter segments of both totally double-stranded and single strand-containing replicating molecules varied in length from about 3 to about 80% of the circular contour length of the molecule. Similar classes of replicating molecules were found in mtDNA from regenerating rat liver and chick embryos, indicating them to be normal intermediates in the replication of mtDNA All of the mtDNAs examined included partially single-stranded simple (nonforked) circular molecules. A possible scheme for the replication of mtDNA is presented, based on the different molecular forms observed
Full Text
The Full Text of this article is available as a PDF (1.9 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnberg A., van Bruggen E. F., Borst P. The presence of DNA molecules with a displacement loop in standard mitochondrial DNA preparations. Biochim Biophys Acta. 1971 Aug 26;246(2):353–357. doi: 10.1016/0005-2787(71)90147-x. [DOI] [PubMed] [Google Scholar]
- Bode H. R., Morowitz H. J. Size and structure of the Mycoplasma hominis H39 chromosome. J Mol Biol. 1967 Jan 28;23(2):191–199. doi: 10.1016/s0022-2836(67)80026-3. [DOI] [PubMed] [Google Scholar]
- Chang J. P., Gibley C. W., Jr, Ichinoe K. Establishment of transplantable hepatomas induced by 3'-methyl-4-dimethylaminoazobenzene with special reference to the histologic features of the transplants of early passages. Cancer Res. 1967 Nov;27(11):2065–2071. [PubMed] [Google Scholar]
- Clayton D. A., Smith C. A., Jordan J. M., Teplitz M., Vinograd J. Occurrence of complex mitochondrial DNA in normal tissues. Nature. 1968 Dec 7;220(5171):976–979. doi: 10.1038/220976a0. [DOI] [PubMed] [Google Scholar]
- Gross N. J., Rabinowitz M. Synthesis of new strands of mitochondrial and nuclear deoxyribonucleic acid by semiconservative replication. J Biol Chem. 1969 Mar 25;244(6):1563–1566. [PubMed] [Google Scholar]
- HOTTA Y., BASSEL A. MOLECULAR SIZE AND CIRCULARITY OF DNA IN CELLS OF MAMMALS AND HIGHER PLANTS. Proc Natl Acad Sci U S A. 1965 Feb;53:356–362. doi: 10.1073/pnas.53.2.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirt B. Replicating molecules of polyoma virus DNA. J Mol Biol. 1969 Feb 28;40(1):141–144. doi: 10.1016/0022-2836(69)90302-7. [DOI] [PubMed] [Google Scholar]
- Inman R. B. A denaturation map of the lambda phage DNA molecule determined by electron microscopy. J Mol Biol. 1966 Jul;18(3):464–476. doi: 10.1016/s0022-2836(66)80037-2. [DOI] [PubMed] [Google Scholar]
- Inman R. B., Schnös M. Structure of branch points in replicating DNA: presence of single-stranded connections in lambda DNA branch points. J Mol Biol. 1971 Mar 14;56(2):319–325. doi: 10.1016/0022-2836(71)90467-0. [DOI] [PubMed] [Google Scholar]
- Inselburg J., Fuke M. Replicating DNA: structure of colicin factor E1. Science. 1970 Aug 7;169(3945):590–592. doi: 10.1126/science.169.3945.590. [DOI] [PubMed] [Google Scholar]
- Jaenisch R., Mayer A., Levine A. Replicating SV40 molecules containing closed circular template DNA strands. Nat New Biol. 1971 Sep 15;233(37):72–75. doi: 10.1038/newbio233072a0. [DOI] [PubMed] [Google Scholar]
- Kasamatsu H., Robberson D. L., Vinograd J. A novel closed-circular mitochondrial DNA with properties of a replicating intermediate. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2252–2257. doi: 10.1073/pnas.68.9.2252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meinke W., Goldstein D. A. Studies on the structure and formation of polyoma DNA replicative intermediates. J Mol Biol. 1971 Nov 14;61(3):543–563. doi: 10.1016/0022-2836(71)90064-7. [DOI] [PubMed] [Google Scholar]
- Nass S. Incorporation of 33Pi into mitochondrial and nuclear DNA in regenerating liver. Biochim Biophys Acta. 1967 Aug 22;145(1):60–67. doi: 10.1016/0005-2787(67)90654-5. [DOI] [PubMed] [Google Scholar]
- Ogawa T., Tomizawa J. I., Fuke M. Replication of bacteriophage DNA, II. Structure of replicating DNA of phage lambda. Proc Natl Acad Sci U S A. 1968 Jul;60(3):861–865. doi: 10.1073/pnas.60.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parsons J. A., Rustad R. C. The distribution of DNA among dividing mitochondria of Tetrahymena pyriformis. J Cell Biol. 1968 Jun;37(3):683–693. doi: 10.1083/jcb.37.3.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reich E., Luck D. J. Replication and inheritance of mitochondrial DNA. Proc Natl Acad Sci U S A. 1966 Jun;55(6):1600–1608. doi: 10.1073/pnas.55.6.1600. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SUEOKA N., CHENG T. Y. Fractionation of nucleic acids with the methylated albumin column. J Mol Biol. 1962 Mar;4:161–172. doi: 10.1016/s0022-2836(62)80048-5. [DOI] [PubMed] [Google Scholar]
- Schneider W. C., Kuff E. L. The isolation and some properties of rat liver mitochondrial deoxyribonucleic acid. Proc Natl Acad Sci U S A. 1965 Dec;54(6):1650–1658. doi: 10.1073/pnas.54.6.1650. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vinograd J., Lebowitz J. Physical and topological properties of circular DNA. J Gen Physiol. 1966 Jul;49(6):103–125. doi: 10.1085/jgp.49.6.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Westmoreland B. C., Szybalski W., Ris H. Mapping of deletions and substitutions in heteroduplex DNA molecules of bacteriophage lambda by electron microscopy. Science. 1969 Mar 21;163(3873):1343–1348. doi: 10.1126/science.163.3873.1343. [DOI] [PubMed] [Google Scholar]
- Wolstenholme D. R., Dawid I. B., Ristow H. An electron microscope study of DNA molecules from Chironomus tentans and Chironomus thummi. Genetics. 1968 Dec;60(4):759–770. doi: 10.1093/genetics/60.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolstonholme D. R., Kirschner R. G., Gross N. J. Heart denaturation studies of rat liver mitrochondrial DNA. A denaturation map and changes in molecular configurations. J Cell Biol. 1972 May;53(2):393–406. doi: 10.1083/jcb.53.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ter Schegget J., Borst P. DNA synthesis by isolated mitochondria. II. Detection of product DNA hydrogen-bonded to closed duplex circles. Biochim Biophys Acta. 1971 Aug 26;246(2):249–257. [PubMed] [Google Scholar]