Helicase

Helicases are enzymes that occur in all living organisms and most viruses, and alter the structure of double-stranded nucleic acids. Usually they dissolve the base-pairing of the double stranded DNA or RNA strands. But secondary structures of nucleic acids can be the target of helicases. Depending on the substrate, a distinction between DNA and RNA helicases. They are essential in the replication, transcription, DNA repair and recombination. As explorers applies the Heidelberg Hartmut Hoffmann- Berling.

Function

DNA helicases play a major role, where they initiate the duplication of DNA by the unwinding of the single strands, especially in the replication of the genome; as well as in eukaryotic transcription of mRNA from DNA, where they prepare the copying of DNA by RNA polymerase.

RNA helicases are essential in almost all processes in RNA metabolism: the transcription, the RNA processing (e.g., splicing, or ribosomal biogenesis of subunits), the translation and RNA degradation. They use the energy from the hydrolysis of NTPs usually to melt double-stranded regions in the DNA or RNA secondary structure ( ie dissolve the base pairing ). This function of the enzymes can be reproduced in vitro on artificial substrates. Essential for this is a specific for the group of RNA helicases motif in its helicase - domain. Because of small sequence differences in this design RNA helicases are divided into different families, such as DEAD -box and DEHxD -box helicases. Moreover, it was demonstrated that RNA helicases, in some cases, not only can unwind RNA base pairs, but are also capable of dissolving the interaction of proteins with RNA. One speaks in this context of RNP - remodeling.

Classification

Helicases are grouped according to their amino acid sequence in five superfamilies (SF1 - SF5 ). It is assumed that express both the evolutionary relationship and structural similarities in this grouping. Examples within the family are:

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

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 inhibition of the enzyme may be ( helicase primase inhibitors) eg herpes viruses based on new therapeutics.

Further Reading

• James A. Borowiec: DNA Helicases. In: Melvin L. DePamphilis (ed.) DNA replication in eukaryotic cells. CSHL Press, 1996, ISBN 0879694599, 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 0125400705, pp. 78-118.
• CL Mandahar: Multiplication of RNA viruses plans. Springer, 2006, ISBN 140204724X, 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 11,839,499th
• Gorbalenya A. E. 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 ).