DNA replication is the process of copying genetic material. It's a crucial step in cell division, ensuring each new cell gets an exact copy of the original DNA. This topic dives into the nitty-gritty of how it all happens.
We'll look at the steps of replication, the enzymes involved, and how cells make sure the copies are accurate. Understanding this process is key to grasping how genes are passed on and how mutations can occur.
DNA Replication Process
Initiation
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The Nucleus and DNA Replication | Anatomy and Physiology I View original
DNA replication is initiated at specific sites called origins of replication during the S phase of the cell cycle
Helicase enzymes unwind the double helix, creating a replication fork with two single-stranded templates
Topoisomerases relieve the tension and supercoiling caused by the unwinding of the DNA helix
Elongation
During elongation, DNA polymerases synthesize new strands complementary to the single-stranded templates in a 5' to 3' direction
The leading strand is synthesized continuously in the direction of the replication fork
The lagging strand is synthesized discontinuously as Okazaki fragments in the opposite direction of the replication fork
RNA primers, synthesized by primase, are required for DNA polymerases to initiate synthesis of new strands
Termination
Termination occurs when two replication forks meet (in prokaryotes) or when the replication fork reaches the end of the linear chromosome (in eukaryotes)
The newly synthesized fragments are joined by DNA ligase, which seals the nicks between Okazaki fragments and the continuous leading strand
Enzymes in DNA Replication
Unwinding and Separating DNA Strands
Helicase unwinds the double helix and separates the DNA strands, creating single-stranded templates for replication
Topoisomerases relieve the tension and supercoiling caused by the unwinding of the DNA helix, preventing the formation of knots and tangles
Synthesizing New DNA Strands
Primase synthesizes short RNA primers (8-12 nucleotides) complementary to the single-stranded DNA templates, providing a starting point for DNA synthesis
DNA polymerases (III and I in prokaryotes, α, δ, and ε in eukaryotes) catalyze the addition of nucleotides to the growing DNA strand in a 5' to 3' direction
DNA polymerases also proofread and correct errors during replication, ensuring high fidelity
Joining and Sealing DNA Fragments
DNA ligase joins the Okazaki fragments on the lagging strand and seals nicks in the newly synthesized DNA
In eukaryotes, DNA ligase also seals the gaps between the newly synthesized DNA and the RNA primers, which are later replaced by DNA polymerase
Semiconservative Replication
Process and Outcome
During semiconservative replication, the two strands of the original DNA molecule separate, and each strand serves as a template for the synthesis of a new complementary strand
The newly synthesized DNA molecules consist of one original (parental) strand and one newly synthesized (daughter) strand
This process results in two identical DNA molecules, each containing one original and one new strand
Experimental Evidence
The semiconservative nature of DNA replication was demonstrated by the Meselson-Stahl experiment
They used density labeling with heavy nitrogen (15N) to distinguish between original and newly synthesized DNA strands
Ultracentrifugation was used to separate DNA molecules based on their density, confirming the presence of hybrid DNA molecules after one round of replication
Significance
The semiconservative nature of DNA replication ensures that genetic information is accurately passed on to daughter cells during cell division
This mechanism maintains the integrity of the genetic material across generations and is essential for the continuity of life
Fidelity of DNA Replication
Complementary Base Pairing
The complementary base pairing rules (A-T and G-C) ensure that the newly synthesized strands are accurate copies of the original template strands
The specific hydrogen bonding between complementary bases minimizes the occurrence of mismatched base pairs
Proofreading by DNA Polymerases
DNA polymerases have proofreading ability, which allows them to detect and correct mismatched nucleotides during replication
The 3' to 5' exonuclease activity of DNA polymerases enables the removal of incorrectly incorporated nucleotides
This proofreading function significantly reduces the error rate of DNA replication (from 1 in 10^4 to 1 in 10^7 nucleotides)
Mismatch Repair Systems
Mismatch repair systems recognize and correct mismatched base pairs that escape the proofreading function of DNA polymerases
These systems scan the newly synthesized DNA for mismatches and repair them by excising the incorrect nucleotide and replacing it with the correct one
Examples of mismatch repair systems include the MutHLS system in prokaryotes and the MSH/MLH system in eukaryotes
Importance of High Fidelity
The high fidelity of DNA replication is essential for maintaining genomic stability and preventing mutations that can lead to genetic disorders or cancer
Accurate DNA replication ensures the faithful transmission of genetic information across generations, which is crucial for the survival and evolution of species