How many enzymes and other proteins participate in DNA replication?

• A. Only two.
• B. Five.
• C. More than a dozen.
• D. Dozens.

Answer: (C)

DNA replication is carried out by a multiprotein machine known as the replisome, which brings together many enzymes and accessory proteins to carry out all the steps required: unwinding the DNA, priming, synthesis, proofreading, and processing of Okazaki fragments on the lagging strand. You need helicase to unwind the double helix, single-strand DNA-binding proteins to keep the template open, primase to lay down RNA primers, DNA polymerases to synthesize new DNA, sliding clamps and clamp loaders to keep the polymerases on the DNA with high processivity, and topoisomerases to relieve the twisting strain that results from unwinding. On the lagging strand, additional enzymes remove primers and join fragments, and ligases seal the resulting nicks. Beyond the core synthesis and processing enzymes, there are numerous regulatory and coordinating factors that help initiate replication at origins and coordinate the activity of the replisome with the cell cycle.

Because all these distinct roles require separate proteins, the total number of participants is well over a dozen. In bacteria, the core replisome already involves roughly a dozen to twenty distinct components; in eukaryotes, the assembly is even more elaborate, with many more proteins contributing to a functioning replication fork. Therefore, more than a dozen is the best description of how many factors participate in DNA replication.