Helicases As Molecular Motors: An Insight

Overview

Journal Physica A

Date 2020 Apr 15

PMID 32288077

Citations 7

Authors

Narendra Tuteja

Renu Tuteja

Affiliations

Soon will be listed here.

Abstract

Helicases are one of the smallest motors of biological system, which harness the chemical free energy of ATP hydrolysis to catalyze the opening of energetically stable duplex nucleic acids and thereby are involved in almost all aspect of nucleic acid metabolism including replication, repair, recombination, transcription, translation, and ribosome biogenesis. Basically, they break the hydrogen bonding between the duplex helix and translocate unidirectionally along the bound strand. Mostly all the helicases contain some conserved signature motifs, which act as an engine to power the unwinding. After the discovery of the first prokaryotic DNA helicase from bacteria in 1976 and the first eukaryotic one from the lily plant in 1978, many more (>100) have been isolated. All the helicases share some common properties, including nucleic acid binding, NTP hydrolysis and unwinding of the duplex. Many helicases have been crystallized and their structures have revealed an underlying common structural fold for their function. The defects in helicases gene have also been reported to be responsible for variety of human genetic disorders, which can lead to cancer, premature aging or mental retardation. Recently, a new role of a helicase in abiotic stress signaling in plant has been discovered. Overall, helicases act as essential molecular tools for cellular machinery and help in maintaining the integrity of genome. Here an overview of helicases has been covered which includes history, biochemical assay, properties, classification, role in human disease and mechanism of unwinding and translocation.

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References

Tuteja N, Singh M, Misra M, Bhalla P, Tuteja R . Molecular mechanisms of DNA damage and repair: progress in plants. Crit Rev Biochem Mol Biol. 2001; 36(4):337-97. DOI: 10.1080/20014091074219. View

Pause A, Sonenberg N . Mutational analysis of a DEAD box RNA helicase: the mammalian translation initiation factor eIF-4A. EMBO J. 1992; 11(7):2643-54. PMC: 556740. DOI: 10.1002/j.1460-2075.1992.tb05330.x. View

Velankar S, Soultanas P, Dillingham M, Subramanya H, Wigley D . Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism. Cell. 1999; 97(1):75-84. DOI: 10.1016/s0092-8674(00)80716-3. View

Zhang S, Grosse F . Nuclear DNA helicase II unwinds both DNA and RNA. Biochemistry. 1994; 33(13):3906-12. DOI: 10.1021/bi00179a016. View

Dillingham M, Spies M, Kowalczykowski S . RecBCD enzyme is a bipolar DNA helicase. Nature. 2003; 423(6942):893-7. DOI: 10.1038/nature01673. View

Yarranton G, Gefter M . Enzyme-catalyzed DNA unwinding: studies on Escherichia coli rep protein. Proc Natl Acad Sci U S A. 1979; 76(4):1658-62. PMC: 383449. DOI: 10.1073/pnas.76.4.1658. View

Sengupta D, Borowiec J . Strand-specific recognition of a synthetic DNA replication fork by the SV40 large tumor antigen. Science. 1992; 256(5064):1656-61. DOI: 10.1126/science.256.5064.1656. View

Hsieh J, Moore K, Lohman T . A two-site kinetic mechanism for ATP binding and hydrolysis by E. coli Rep helicase dimer bound to a single-stranded oligodeoxynucleotide. J Mol Biol. 1999; 288(2):255-74. DOI: 10.1006/jmbi.1999.2666. View

Delagoutte E, von Hippel P . Helicase mechanisms and the coupling of helicases within macromolecular machines. Part I: Structures and properties of isolated helicases. Q Rev Biophys. 2003; 35(4):431-78. DOI: 10.1017/s0033583502003852. View

10.

Tuteja N, Tuteja R, Rahman K, Kang L, Falaschi A . A DNA helicase from human cells. Nucleic Acids Res. 1990; 18(23):6785-92. PMC: 332732. DOI: 10.1093/nar/18.23.6785. View

11.

Tuteja N, Beven A, Shaw P, Tuteja R . A pea homologue of human DNA helicase I is localized within the dense fibrillar component of the nucleolus and stimulated by phosphorylation with CK2 and cdc2 protein kinases. Plant J. 2001; 25(1):9-17. DOI: 10.1046/j.1365-313x.2001.00918.x. View

12.

Walker J, Saraste M, Runswick M, Gay N . Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1982; 1(8):945-51. PMC: 553140. DOI: 10.1002/j.1460-2075.1982.tb01276.x. View

13.

Mechanic L, Hall M, Matson S . Escherichia coli DNA helicase II is active as a monomer. J Biol Chem. 1999; 274(18):12488-98. DOI: 10.1074/jbc.274.18.12488. View

14.

Venkatesan M, Silver L, Nossal N . Bacteriophage T4 gene 41 protein, required for the synthesis of RNA primers, is also a DNA helicase. J Biol Chem. 1982; 257(20):12426-34. View

15.

Delagoutte E, von Hippel P . Helicase mechanisms and the coupling of helicases within macromolecular machines. Part II: Integration of helicases into cellular processes. Q Rev Biophys. 2003; 36(1):1-69. DOI: 10.1017/s0033583502003864. View

16.

Lindahl T, Wood R . Quality control by DNA repair. Science. 1999; 286(5446):1897-905. DOI: 10.1126/science.286.5446.1897. View

17.

Constantinesco F, Forterre P, Koonin E, Aravind L, Elie C . A bipolar DNA helicase gene, herA, clusters with rad50, mre11 and nurA genes in thermophilic archaea. Nucleic Acids Res. 2004; 32(4):1439-47. PMC: 390275. DOI: 10.1093/nar/gkh283. View

18.

Tuteja N, Tuteja R . Prokaryotic and eukaryotic DNA helicases. Essential molecular motor proteins for cellular machinery. Eur J Biochem. 2004; 271(10):1835-48. PMC: 7164108. DOI: 10.1111/j.1432-1033.2004.04093.x. View

19.

Hotta Y, Stern H . DNA unwinding protein from meiotic cells of Lilium. Biochemistry. 1978; 17(10):1872-80. DOI: 10.1021/bi00603a011. View

20.

Laurent B, Treitel M, Carlson M . Functional interdependence of the yeast SNF2, SNF5, and SNF6 proteins in transcriptional activation. Proc Natl Acad Sci U S A. 1991; 88(7):2687-91. PMC: 51303. DOI: 10.1073/pnas.88.7.2687. View