1. CDK and cyclins The progression of cell cycle is catalyzed by cyclin-dependent kinase (CDK) which, as the name suggests, is activated by a special class of proteins called cyclins. In mammals, different cyclins are designated as A, B, C, D and so on. In budding yeast (S. cerevisiae), nine cyclins have been identified: Cln1 to Cln3 and Clb1 to Clb6.

2. The cyclin-CDK complexes involved in each phase of the cell cycle. The red line indicates the timing a particular complex is involved.

6. Topoisomerases Structure of the Topo I/DNA complex.

7. There are two types of topoisomerases: type I produces transient single-strand breaks in DNA and types II produces transient double-strand breaks. As a result, the type I enzyme removes supercoils from DNA one at a time, whereas the type II enzyme removes supercoils two at a time. Although the type II topoisomerase is more efficient in removing supercoils, this enzyme requires the energy from ATP hydrolysis, but the type I topoisomerase does not.

8. Without topoisomerases, the DNA cannot replicate normally. Therefore, the inhibitors of topoisomerases have been used as anti-cancer drugs to stop the proliferation of malignant cells. However, these inhibitors may also stop the division of normal cells. Some cells (e.g., hair cells) which need to continuously divide will be most affected. This explains a noticeable side effect: the hair loss.

9. . Figure: Schematic drawing of the DNA replication process. O1, O2, and O3 are replication origins, each serving a region called replicon (R1, R2, and R3). DNA replication involves unwinding of the double helix. New strands are synthesized by DNA polymerases using the old strands as template. Unwinding of a DNA molecule looks like a "fork" growing in one direction. The region being replicated looks like a bubble called the "replication bubble" (in red).

10. In eukaryotic DNA, the fork movement is only about 100 bp per second. This is probably due to the association of DNA with histones, which may hinder the fork movement. In humans, replication of the entire genome requires about 8 hours. In fruit flies, it takes only 3 - 4 minutes.

11. Based on computer analysis, the consensus sequence of human replication origin is WAWTTDDWWWDHWGWHMAWTT, where W = A or T; D = A, G or T ; H = A, C or T, and M = A or C. Note that "A" and "T" dominate the replication origin.

12. MECHANISM OF DNA REPLICATION  DNA molecules are synthesized by DNA polymerases from deoxyribonucleoside triphosphate (dNTP).  DNA polymerases can extend nucleic acid strands only in the 5' to 3' direction.  The two strands in a DNA molecule are antiparallel. Therefore, only one strand (leading strand) can be synthesized continuously by the DNA polymerase. The other strand (lagging strand) is synthesized segment by segment.

13. There are five types of DNA polymerases in mammalian cells: a, b, g, d, and e. The g subunit is located in the mitochondria, responsible for the replication of mtDNA. Other subunits are located in the nucleus. Their major roles are given below: a: synthesis of lagging strand. b: DNA repair. d: synthesis of leading strand. e: DNA repair.

14. Steps in the synthesis of the lagging strand.

15. Telomerase and Aging Synthesis of the lagging strand requires a short primer which will be removed. At the extreme end of a chromosome, there is no way to synthesize this region when the last primer is removed. Therefore, the lagging strand is always shorter than its template by at least the length of the primer. This is the so-called "end-replication problem". Bacteria do not have the end-replication problem, because its DNA is circular. In eukaryotes, the chromosome ends are called telomeres which have at least two functions:  to protect chromosomes from fusing with each other.  to solve the end-replication problem.

16. Telomerase and telomere extension. To extend the length of a telomere, the telomerase first extends its longer strand. Then, using the same mechanism as synthesizing the lagging strand, the shorter strand is extended.

17. The mechanism of telomere extension by telomerase