Helicases

Structure of E. coli helicase RuvA

Helicases are enzymes that are found in all living things and most viruses and that change the structure of double-stranded nucleic acids . Usually they break up the base pairing of double strands of DNA or RNA. Even secondary structures of nucleic acids can be the target of helicases. Depending on the substrate, a distinction is made between DNA and RNA helicases. They are essential for replication , DNA repair and recombination . Hartmut Hoffmann-Berling from Heidelberg is considered the discoverer .

function

Above all, DNA helicases play a crucial role in the replication of the genome: they unwind the single strands of DNA before they are doubled by replication. The Mcm complex serves as a replicative helicase for eukaryotes. Helicases also open up eukaryotic transcription by preparing the DNA for mRNA to be copied by the RNA polymerase.

RNA helicases are essential in almost all processes in RNA metabolism: transcription , RNA processing (e.g. splicing or the biogenesis of ribosomal subunits), translation and RNA degradation. They usually use the energy from the hydrolysis of the NTPs to melt double-stranded areas in the DNA or RNA secondary structure (i.e. to break up the base pairing). This function of the enzymes can be reproduced in vitro on artificial substrates. A motif specific for the group of RNA helicases in their helicase domain is essential for this. Due to small sequence differences in this motif, RNA helicases are divided into different families, e.g. B. DEAD-box and DEHxD-box helicases. In addition, it could be shown that in some cases RNA helicases can not only unwind RNA base pairings, but are also able to resolve the interaction of proteins with RNA. In this context, one speaks of RNP remodeling.

classification

Helicases are divided into five superfamilies (SF1-SF5) based on their amino acid sequence . It can be assumed that this grouping expresses both the evolutionary relationship and structural similarities. Examples within families are:

• SF1 / 2 : DEAD box RNA helicases such as eIF4A , DEAH box RNA helicases , the TFIIH helicases XPB and XPD associated with the transcription factor IIH , as well as other eukaryotic, bacterial and viral helicases
• SF3 : mainly helicases in small RNA and DNA viruses
• SF4 : the hexameric dnaB proteins in bacterial primosomes

medicine

A helicase defect is the cause of Werner syndrome . In addition to the diseases due to the lack of or insufficient activity of the helicase, the inhibition of the enzyme z. B. be the basis of new therapeutic agents for herpes viruses (helicase primase inhibitors).

further reading

• James A. Borowiec: DNA Helicases . In: Melvin L. DePamphilis (Ed.): DNA replication in eukaryotic cells . CSHL Press, 1996, ISBN 0-87969-459-9 , pp. 545-574 .
• Boriana Martintcheva and Sandra K. Weller: A Tale of Two HSV-1 Helicases: Role of Phage and Animal Virus Helicases in DNA Replication and Recombination . In: Kivie Moldave (Ed.): Progress in nucleic acid research and molecular biology 70 . Academic Press, 2001, ISBN 0-12-540070-5 , pp. 78-118 .
• CL Mandahar: Multiplication of RNA plant viruses . Springer, 2006, ISBN 1-4020-4724-X , pp. 151-165 .
• Caruthers JM, McKay DB: Helicase structure and mechanism . In: Curr. Opin. Struct. Biol . 12, No. 1, February 2002, pp. 123-33. PMID 11839499 .
• Gorbalenya AE and Koonin EV: Helicases: amino acid sequence comparisons and structure-function relationships. Curr. Opin. Struct. Biol. 3: 419-429 (1993). doi : 10.1016 / S0959-440X (05) 80116-2
• Mackintosh SG, Raney KD: DNA unwinding and protein displacement by superfamily 1 and superfamily 2 helicases . In: Nucleic Acids Res . 34, No. 15, 2006, pp. 4154-9. doi : 10.1093 / nar / gkl501 . PMID 16935880 . PMC 1616963 (free full text).

Individual evidence

1. ↑ Mahmoud Abdel-Monem, Hildegard Dürwald, Hartmut Hoffmann-Berling: Enzymic unwinding of DNA: 2. Chain separation by an ATP-dependent DNA unwinding enzyme. In: Eur J Biochem 65, 2, 1976: 441-449. doi: 10.1111 / j.1432-1033.1976.tb10359.x
2. ↑ ML Bochman, A. Schwacha: The Mcm complex: unwinding the mechanism of a replicative helicase. In: Microbiology and molecular biology reviews: MMBR. Volume 73, number 4, December 2009, pp. 652-683, doi : 10.1128 / MMBR.00019-09 , PMID 19946136 , PMC 2786579 (free full text) (review). Mcm: acronym for mini chromosome maintenance . Generalized: Mcm helicases contribute to genomic stability.
3. ↑ Superfamilies 1 and 2 helicase domain profiles .
4. ↑ Superfamilies 3 helicase domain profiles .
5. ↑ Superfamilies 4 helicase domain profiles .