The first molecule active during DNA replication is helicase.

Here's why:

* Helicase's Role: Helicase is an enzyme that "unzips" the DNA double helix by breaking the hydrogen bonds between the nitrogenous bases. This creates two separate strands, known as the leading and lagging strands.

* Initiation of Replication: Before any other enzymes can access the DNA, the double helix needs to be unwound. Helicase initiates this process, making it the first critical step in DNA replication.

Let me know if you'd like to learn more about other molecules involved in DNA replication!