Replicative Helicases

Helicase is an enzyme that unwinds and separates the two strands of DNA, enabling the genetic information stored in DNA to be copied during DNA replication.

Why is DNA Unwinding Necessary?

DNA normally exists as a double helix, in which complementary bases on the two strands are held together by hydrogen bonds. Before replication can occur, these two strands must be separated so that each strand can serve as a template for the formation of a new strand.

ATP-Driven Activity

Replicative helicases are loaded onto DNA at or near specific regions called replication origins. They use energy generated through nucleotide hydrolysis, particularly ATP hydrolysis, to move along DNA and separate its two strands.

Formation of Replication Fork

As the helicase moves along the DNA molecule, it disrupts the interactions between complementary base pairs and exposes the individual strands. This unwinding produces a Y-shaped structure called the replication fork, where DNA replication takes place.

Role of Topoisomerases

The unwinding of DNA creates torsional stress and supercoiling ahead of the replication fork. Topoisomerases help relieve this stress by controlling DNA twisting, thereby preventing excessive supercoiling, tangling and DNA breakage.

Formation of New DNA

Once the parental DNA strands are separated, each strand acts as a template for the synthesis of a new complementary DNA strand. This enables the genetic information to be accurately copied.

MCM2–7 and CMG Helicase

DNA replication is carefully regulated so that it begins at the correct stage of the cell cycle. Replicative helicases are initially present as inactive MCM2–7 double hexamers at replication origins.

During activation, these structures are remodelled into the active CMG helicase complex, composed of Cdc45, MCM2–7 and GINS. The activation of CMG helicase is closely linked to the initial melting and unwinding of DNA, allowing the replication machinery to establish the replication fork.