What is the Difference Between SF1 and SF2

The key difference between SF1 and SF2 is their ability to unwind nucleic acids. While SF1 only unwinds DNA, SF2 unwinds both DNA and RNA.

Helicase is one of the key enzymes that take part in the DNA replication process as well as in DNA repair processes. The primary role of helicase is to take part in the unwinding process in order to facilitate the separation of double-stranded DNA molecules. The enzyme’s activity is essential during the initiation phase of DNA replication. Helicases are divided as Super Family 1 and Super Family 2 primarily based on their structural differences. Within each Super Family, there are more diverse types of helicases.


1. Overview and Key Difference
2. What is SF1  
3. What is SF2
4. Similarities – SF1 and SF2
5. SF1 vs SF2 in Tabular Form
6. Summary – SF1 vs SF2

What is SF1?

Super Family 1 helicase is a type of helicase that comprises a hexameric structure alongside the internal core protein, which depicts helicase activity. SF1 helicase is one of the largest classes of helicase and can be further categorized as SF1A helicases and SF1B helicases. Proteins such as PcrA, Rep and UvrD, belong to the class of SF1A helicases. In comparison, proteins like RecA and Dda belong to the class of SF1B helicases. The functions of SF1 helicases vary widely. Some of the vital functions of SF1 helicases include DNA replication, DNA recombination, Okazaki fragment processing, telomere formation, and nucleotide excision repair of DNA damage. In some bacterial species, SF1 type of helicases also takes part in helping horizontal gene transfer via conjugation. Furthermore, in viruses, SF1 helicases aid in viral replication.

Figure 01: Helicase Action

There are many different motifs associated with the structure of SF1 helicases. They contain at least 7 conserved motifs among all the different types of SF1 helicases (Q, I, Ia, II, III, IV, V, and VI). The structure of SF1 helicase is a crystal, where the motifs are clustered together. There is a characteristic ATP binding pocket between the motifs and the DNA binding site. The non-conserved domains are distributed to maintain the structural integrity of the helicase molecule. These domains could vary between the SF1A helicases and SF1B helicases.

What is SF2?

Super family 2 helicase is one of the most diverse groups of helicase superfamilies. There are many types of SF2 helicases such as RecQ-like helicases, RecG – like helicases, Rad3/XPD and NS3 helicases. Some restriction enzymes, such as type I restriction enzymes, also fall under this category. The general function of SF2 helicases is the unwinding of double-stranded DNA. However, some types of SF2 helicases do not have the ability to completely act as helicase enzymes. SF2 helicases are widely used in RNA processing as well. The DEAD-box family of SF2 helicases take part in RNA processing, including transcription, splicing, translation processing and RNA-protein complex assembly.

Figure 02: Helicase

The structure of SF2 helicase also contains conserved motifs. However, some domains differ slightly from that of SF1 helicase. They also contain an ATP binding domain apart from the DNA binding domain.

What are the Similarities Between SF1 and SF2?

  • SF1 and SF2 show helicase activity.
  • Moreover, both take part in DNA replication and recombination.
  • SF1 and SF2 are composed of conserved motifs.
  • Both have an ATP binding domain and a DNA binding domain.
  • These forms are multi-domain proteins.
  • Moreover, if mutations take place in either type, it will result in deleterious effects.
  • Both SF1 and SF2 are crucial to ensure the continuity of the cell cycle.
  • SF1 and SF2 are found in prokaryotes as well as in eukaryotes.

What is the Difference Between SF1 and SF2?

SF1 and SF2 are two super families of helicase. They show a wide diversity. The key difference between SF1 and SF2 is that SF1 is primarily involved in the unwinding of DNA, while SF2 also takes part in RNA processing during transcription and translation. When comparing the different motifs of the protein, SF1 and SF2 primarily differ based on motif III and motif IV. Even though they have a structural similarity, SF1 helicases form toroidal hexameric structures while SF2 does not form these structural arrangements.

Another difference between SF1 and SF2 is that SF1 helicases prefer adenine nucleotides more, while SF2 helicases prefer all five nucleotides to target for unwinding. When comparing the unwinding direction, SF1 helicases only translocate in the 5’ to 3’ direction, while SF2 helicases have the ability to translocate along with the nucleic acids in both directions.

The below infographic presents the differences between SF1 and SF2 in tabular form for side by side comparison.

Summary – SF1 vs SF2

Helicases are a very important and diverse group of enzymes that take part in DNA replication. However, due to its high diversity, enzymes are categorized into superfamilies. SF1 and SF2 are the two largest super families of helicases. While SF1 is primarily associated with processing related to DNA, SF2 is associated with both DNA and RNA processing. Thus, this is the key difference between SF1 and SF2. Furthermore, SF1 and SF2 also differ in their structural arrangement as SF2 does not form hexameric structures. Mutations in the SF1 and SF2 helicases will lead to the development of cancer following dysregulation of the cell cycle and other vital mechanisms such as DNA repair.