DNA Replication and Cell Division

When a cell divides, its DNA is accurately doubled (replicated) and distributed to the daughter cells. The precision of this DNA replication is the foundation of heredity.

Basic Knowledge

The basic principle of DNA replication is semiconservative replication. Double-stranded DNA unwinds into two separate strands, and each strand serves as a template for the synthesis of a complementary new strand. As a result, two double helices are formed, each containing one original strand.
Steps of replication:
① Helicase cleaves DNA (unwinds the helix).
② DNA polymerase polymerizes complementary nucleotides according to the template in the 5'→3' direction.
③ DNA ligase joins the fragments (Okazaki fragments).
Semiconservative replication was demonstrated in 1958 by Meselson and Stahl through an ¹⁵N-labeling experiment. This classic experiment measured three types of DNA distribution—light, heavy, and intermediate—by mass analysis.
Cell division cycle:
・Interphase (G1→S→G2): The cell grows, and DNA is replicated during S phase.
・Mitotic phase (M phase): Chromosomes condense and are distributed to daughter cells (prophase, metaphase, anaphase, and telophase).

Further Study

Because DNA polymerase can synthesize DNA only in the 5'→3' direction, both strands cannot be synthesized continuously in the same direction. Okazaki fragments solve this problem. One strand, the leading strand, is synthesized continuously, whereas the other, the lagging strand, is synthesized discontinuously as short fragments (Okazaki fragments), which are later joined by DNA ligase. This internationally recognized achievement was discovered in 1968 by the Japanese couple Reiji and Tsuneko Okazaki.
The error rate of DNA replication is remarkably low—about one error per billion bases. This accuracy results from the proofreading function of DNA polymerase and repair mechanisms such as mismatch repair. Even highly precise chemical devices have difficulty achieving such accuracy; this demonstrates the strength of biological systems in which multiple enzymes cooperate.
The cell cycle is precisely controlled by proteins such as cyclins and cyclin-dependent kinases (CDKs). Hartwell, Hunt, and Nurse received the 2001 Nobel Prize in Physiology or Medicine for this discovery. Because failure of this control can lead to cancer, it is also an important medical topic.

Points to Note

① Three models were proposed: semiconservative replication (one original strand + one new strand), conservative replication (the original double strand and a new double strand), and dispersive replication (a mosaic pattern). Semiconservative replication was proven correct. ② DNA polymerase works only in the 5'→3' direction. This requires Okazaki fragments on the lagging strand. ③ Do not confuse the roles of helicase (unwinding), polymerase (synthesis), and ligase (joining). ④ In the cell cycle, DNA replication occurs during S phase (interphase); M phase is only for division. DNA replication does not occur during M phase.

Practice

1. What is the method called in which replication produces a double helix consisting of one original strand and one new strand?
2. In which direction does DNA polymerase elongate a DNA strand?
3. During which phase of the cell cycle does DNA replication occur?