8.2

The DNA Replication Fork

24.5K views01:02 min

In the cell, DNA replication always initiates at specific locations on the DNA called the origin of replication.

At the start of replication, the enzyme DNA helicase binds and moves along the DNA strand, unwinding and separating the DNA.

The resulting Y-shaped structure formed by the separate strands of DNA looks like a two-tined fork and becomes a site of DNA replication; therefore, this structure is known as the “Replication Fork”.

These separate, single-stranded DNA molecules are prone to form double-stranded hairpin loops or to rewind with the other strand.

To prevent this from happening, single-strand DNA binding proteins, or SSBs, bind to single-stranded DNA and inhibit rewinding.

Now the exposed single strands of DNA can act as templates for the synthesis of the complementary daughter strands.

Overview

Loading...

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in each direction leading away from the location of the initial opening. In organisms with large genomes, the replication of DNA is not done from a single point of origin but in many distinct, localized replication forks.

The unhindered progression of the replication fork is necessary for complete DNA replication and genome stability; however, the replication fork is often stalled by internal or external factors that can slow or stop its progression, resulting in replication stress. Replication stress causes genomic instability, which is a hallmark of diseases like cancer. Genomic instability is characterized by genomic alterations and increased frequency of harmful mutations. The movement of the replication fork can stop due to several reasons. For example, the drug hydroxyurea depletes the pool of nucleotides available for incorporation into the daughter strand, stalling the replication fork. Other problems that may hinder the progression of the replication fork include DNA lesions, a collision between a replication fork and a transcription complex, and defects in the enzymes involved in DNA replication.

The cell has a variety of repair mechanisms to reinitiate the stalled replication fork. S-phase checkpoints do not allow cells to begin mitosis until DNA repair is complete. Additionally, fork repriming can restart DNA synthesis by bypassing a DNA lesion or block. Despite these robust mechanisms, sometimes stalled forks cannot be reinitiated, which leads to the collapse of a fork, halting DNA replication.

Transcript

Explore More Videos

DNA Replication

Replication Fork

Molecular Biology

Replication Process

Nucleotide Pairing