Abstract
The regulation of DNA replication at a subchromosomal level in mammalian cells has been investigated. DNA fiber autoradiographs were prepared from mouse L-929 cells pulse labeled with (3H)thymidine. Initiation events and subsequent chain growth occurring over short stretches (up to three replication units in length) of chromosomal DNA were analyzed. The results show that adjacent units usually initiate replication synchronously and that this synchrony is related to the proximity of initiation sites. In addition, adjacent units are of similar size and the rates of replication fork progression within units and on adjacent units are similar. The rate of fork progression increases with increasing replication unit size. Finally, no evidence for fixed termination sites for the units has been found. These observations suggest that despite large variations in size of replication units, timing of initiation events, and rates of fork progression found in chromosomal DNA as a whole, these processes are closely regulated within subchromosomal clusters of active replication units.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amaldi F., Buongiorno-Nardelli M., Carnevali F., Leoni L., Mariotti D., Pomponi M. Replicon origins in Chinese hamster cell DNA. II. Reproducibility. Exp Cell Res. 1973 Jul;80(1):79–87. doi: 10.1016/0014-4827(73)90277-2. [DOI] [PubMed] [Google Scholar]
- Blumenthal A. B., Kriegstein H. J., Hogness D. S. The units of DNA replication in Drosophila melanogaster chromosomes. Cold Spring Harb Symp Quant Biol. 1974;38:205–223. doi: 10.1101/sqb.1974.038.01.024. [DOI] [PubMed] [Google Scholar]
- Bostock C. J., Prescott D. M., Hatch F. T. Timing of replication of the satellite and main band DNAs in cells of the kangaroo rat (Dipodomys ordii). Exp Cell Res. 1972 Oct;74(2):487–495. doi: 10.1016/0014-4827(72)90405-3. [DOI] [PubMed] [Google Scholar]
- Callan H. G. Replication of DNA in the chromosomes of eukaryotes. Proc R Soc Lond B Biol Sci. 1972 Apr 18;181(1062):19–41. doi: 10.1098/rspb.1972.0039. [DOI] [PubMed] [Google Scholar]
- Gautschi J. R., Kern R. M., Painter R. B. Modification of replicon operation in HeLa cells by 2,4-dinitrophenol. J Mol Biol. 1973 Nov 5;80(3):393–403. doi: 10.1016/0022-2836(73)90411-7. [DOI] [PubMed] [Google Scholar]
- Hand R., Tamm I. DNA replication: direction and rate of chain growth in mammalian cells. J Cell Biol. 1973 Aug;58(2):410–418. doi: 10.1083/jcb.58.2.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hand R., Tamm I. Initiation of DNA replication in mammalian cells and its inhibition by reovirus infection. J Mol Biol. 1974 Jan 15;82(2):175–183. doi: 10.1016/0022-2836(74)90339-8. [DOI] [PubMed] [Google Scholar]
- Hand R., Tamm I. Rate of DNA chain growth in mammalian cells infected with cytocidal RNA viruses. Virology. 1972 Feb;47(2):331–337. doi: 10.1016/0042-6822(72)90268-1. [DOI] [PubMed] [Google Scholar]
- Hori T., Lark K. G. Effect of puromycin on DNA replication in Chinese hamster cells. J Mol Biol. 1973 Jul 5;77(3):391–404. doi: 10.1016/0022-2836(73)90446-4. [DOI] [PubMed] [Google Scholar]
- Huberman J. A., Riggs A. D. On the mechanism of DNA replication in mammalian chromosomes. J Mol Biol. 1968 Mar 14;32(2):327–341. doi: 10.1016/0022-2836(68)90013-2. [DOI] [PubMed] [Google Scholar]
- Huberman J. A., Tsai A. Direction of DNA replication in mammalian cells. J Mol Biol. 1973 Mar 25;75(1):5–12. doi: 10.1016/0022-2836(73)90525-1. [DOI] [PubMed] [Google Scholar]
- Lark C. G., Consigli R., Toliver A. DNA replication in Chinese hamster cells: evidence for a single replication fork per replicon. J Mol Biol. 1971 Jun 28;58(3):873–875. doi: 10.1016/0022-2836(71)90046-5. [DOI] [PubMed] [Google Scholar]
- McFarlane P. W., Callan H. G. DNA replication in the chromosomes of the chicken, Gallus domesticus. J Cell Sci. 1973 Nov;13(3):821–839. doi: 10.1242/jcs.13.3.821. [DOI] [PubMed] [Google Scholar]
- Painter R. B., Schaefer A. W. Variation in the rate of DNA chain growth through the S phase in HeLa cells. J Mol Biol. 1971 May 28;58(1):289–295. doi: 10.1016/0022-2836(71)90247-6. [DOI] [PubMed] [Google Scholar]