Figures & data
Figure 1. DNA is Replicated at a Fixed Site. DNA origins are prepared for replication by licensing (blue circles; Figs. 2 and 3). During replication, DNA is pulled through the replication machinery, which rests at a fixed site on the nuclear matrix. Newly replicated strands of DNA emerge (red) and remain attached to the nuclear matrix at sites that are not licensed for DNA replication (green circles).
Figure 2. The Need for Licensing in Mammalian DNA Replication. A. DNA is replicated at several hundred thousand independent start sites called origins. B. To ensure that each origin only fires once during S-Phase, each origin is ‘licensed’ by the ORC complex. C. The license is removed when the origin is replicated, and cannot be added to any origins until the next G1 phase.
Figure 3. Licensing of Mammalian Replication Origins. A. ORC2L-5L remain on the origin throughout the cell cycle (the fate of ORC6L is currently unknown). B. Licensing begins with the binding of ORC1L, which C recruits CDC6 and CTD1. D. This complex recruits the DNA helicases MCM2-7, and the origin is fully licensed. E. CDK2/CCNA2 and CDK/CCNE1 initiate the entry into S-phase and the removal of ORC1L, CDC6, and CDT1, thereby preventing new licensing. At this point, a number of other proteins are loaded onto the replication fork. Adapted from Takeda and Dutta [Citation2005].
![Figure 3. Licensing of Mammalian Replication Origins. A. ORC2L-5L remain on the origin throughout the cell cycle (the fate of ORC6L is currently unknown). B. Licensing begins with the binding of ORC1L, which C recruits CDC6 and CTD1. D. This complex recruits the DNA helicases MCM2-7, and the origin is fully licensed. E. CDK2/CCNA2 and CDK/CCNE1 initiate the entry into S-phase and the removal of ORC1L, CDC6, and CDT1, thereby preventing new licensing. At this point, a number of other proteins are loaded onto the replication fork. Adapted from Takeda and Dutta [Citation2005].](/cms/asset/8bf2ff44-878e-4cd7-a290-e5f64eb2bace/iaan_a_505679_f0003_b.jpg)
Figure 4. Experimental Manipulation of Mouse Fertilization to Study DNA Replication and Degradation. A. In fertilization by ICSI or IVF, the female (F) and male (M) pronuclei are fully decondensed by about 4 h, and initiate DNA synthesis simultaneously at about 5.5 h. B. When sperm nuclear halos are injected into ooctyes 3 h after parthenogenetic activation of the oocyte, the male pronucleus initiates DNA synthesis after the female pronucleus. C. When sperm nuclei are treated to induce fragmentation of the paternal genome prior to injection, the male pronuclei develop normally until the initiation of S-phase at which point the DNA is degraded.
