DNA replication

DNA replication is a fundamental biological process crucial for genetic continuity. It occurs before cell division, specifically during the S phase (synthesis phase) of interphase in the cell cycle. This process ensures that each new daughter cell receives a complete and identical set of DNA.

The accepted model for DNA replication is semi-conservative replication. This means that each new DNA molecule contains one strand from the original (parent) DNA molecule and one newly synthesized strand. The semi-conservative nature of DNA replication was experimentally validated by Meselson and Stahl in 1958 using heavy and light nitrogen isotopes (15N and 14N).

Here's a breakdown of the DNA replication process:

• Unwinding and Unzipping: The process begins with the unwinding of the DNA double helix. The enzyme DNA helicase breaks the hydrogen bonds between the complementary base pairs that hold the two polynucleotide strands together. This causes the helix to unwind and form two single strands.

• Template Strands: Each original single strand then acts as a template for the synthesis of a new complementary strand.

• Nucleotide Attraction and Base Pairing: Free-floating DNA nucleotides (which are "activated" by having two extra phosphates) are attracted to their complementary exposed bases on each original template strand. Adenine (A) pairs with Thymine (T) (forming two hydrogen bonds), and Guanine (G) pairs with Cytosine (C) (forming three hydrogen bonds).

• New Strand Synthesis: The enzyme DNA polymerase lines up these free DNA nucleotides and catalyzes the condensation reactions that join them together. This forms the sugar-phosphate backbone of the new DNA strands. Hydrogen bonds then form between the bases of the original and new strands.

• Directionality and Leading/Lagging Strands: DNA polymerase can only add nucleotides to the new strand at its 3' end, meaning the new strand is made in a 5' to 3' direction. Because the two original DNA strands are antiparallel (run in opposite directions), DNA polymerase works differently on each template strand:

  • The leading strand is synthesized continuously in the 5' to 3' direction, moving in the same direction as the unwinding of the DNA.

  • The lagging strand is synthesized discontinuously in short segments called Okazaki fragments. These fragments are then joined together by the enzyme DNA ligase, which forms phosphodiester bonds to create a continuous sugar-phosphate backbone.

• Proofreading: DNA polymerase also plays a role in "proofreading" the new strands, correcting most errors to ensure the new DNA double helix is an exact copy of the original.

DNA molecules are very long and are tightly coiled around proteins called histones to fit into the small space of the cell nucleus, forming chromosomes. In eukaryotic cells, mitochondria and chloroplasts also contain their own DNA, which is circular and shorter, similar to prokaryotic DNA. Prokaryotic DNA, however, is shorter, circular, and not associated with histones (often referred to as 'naked' DNA).

At various points in the cell cycle, DNA is checked for damage. If severe damage is detected, the cell can initiate programmed cell death to prevent issues like tumour growth.