Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/11/04 19:00:45」(JST)

wiki en

In molecular biology and biochemistry, processivity is an enzyme's ability to catalyze "consecutive reactions without releasing its substrate".^[1]

For example, processivity is the average number of nucleotides added by a polymerase enzyme, such as DNA polymerase, per association/disassociation with the template. DNA polymerases associated with DNA replication tend to be highly processive, while those associated with DNA repair tend to have low processivity. Because the binding of the polymerase to the template is the rate-limiting step in DNA synthesis, the overall rate of DNA replication during S phase of the cell cycle is dependent on the processivity of the DNA polymerases performing the replication. DNA clamp proteins are integral components of the DNA replication machinery and serve to increase the processivity of their associated polymerases. Some polymerases add over 50,000 nucleotides to a growing DNA strand before dissociating from the template strand, giving a replication rate of up to 1,000 nucleotides per second.

DNA binding interactions

Polymerases interact with the phosphate backbone and the minor groove of the DNA, so their interactions do not depend on the specific nucleotide sequence. The binding is largely mediated by electrostatic interactions between the DNA and the "thumb" and "palm" domains of the metaphorically hand-shaped DNA polymerase molecule. When the polymerase advances along the DNA sequence after adding a nucleotide, the interactions with the minor groove dissociate but those with the phosphate backbone remain more stable, allowing rapid re-binding to the minor groove at the next nucleotide.

Interactions with the DNA are also facilitated by DNA clamp proteins, which are multimeric proteins that completely encircle the DNA, with which they associate at replication forks. Their central pore is sufficiently large to admit the DNA strands and some surrounding water molecules, which allows the clamp to slide along the DNA without dissociating from it and without loosening the protein-protein interactions that maintain the toroid shape. When associated with a DNA clamp, DNA polymerase is dramatically more processive; without the clamp most polymerases have a processivity of only about 100 nucleotides. The interactions between the polymerase and the clamp are more persistent than those between the polymerase and the DNA. Thus, when the polymerase dissociates from the DNA, it is still bound to the clamp and can rapidly reassociate with the DNA. An example of such a DNA clamp is PCNA (proliferating cell nuclear antigen) found in S. cervesiae.

Polymerase processivities

Multiple DNA polymerases have specialized roles in the DNA replication process. In E. coli, which replicates its entire genome from a single replication fork, the polymerase DNA Pol III is the enzyme primarily responsible for DNA replication and forms a replication complex with extremely high processivity. The related DNA Pol I has exonuclease activity and serves to degrade the RNA primers used to initiate DNA synthesis. Pol I then synthesizes the short DNA fragments that were formerly hybridized to the RNA fragment. Thus Pol I is much less processive than Pol III because its primary function in DNA replication is to create many short DNA regions rather than a few very long regions.

In eukaryotes, which have a much higher diversity of DNA polymerases, the low-processivity initiating enzyme is called Pol α, and the high-processivity extension enzymes are Pol δ and Pol ε. Both prokaryotes and eukaryotes must "trade" bound polymerases to make the transition from initiation to elongation. This process is called polymerase switching.

References

^ Stryer, L.; Berg, J. M.; Tymoczko, J. L. (2002), Biochemistry (5th ed.), New York: W. H. Freeman, ISBN 0716746840 . 27.4.4

Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R. (2004). Molecular Biology of the Gene 5th ed. Benjamin Cummings: Cold Spring Harbor Laboratory Press.

External links

http://opbs.okstate.edu/~melcher/MG/MGW4/MG424.html
http://www.pubmedcentral.gov/articlerender.fcgi?artid=19538
http://www.pubmedcentral.gov/articlerender.fcgi?artid=305186

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. ヒトヘルペスウイルス6型感染症のウイルス学、病因、および疫学 virology pathogenesis and epidemiology of human herpesvirus 6 infection

English Journal

Archaeal DNA polymerases in biotechnology.

Zhang L1, Kang M, Xu J, Huang Y.
Applied microbiology and biotechnology.Appl Microbiol Biotechnol.2015 Aug;99(16):6585-97. doi: 10.1007/s00253-015-6781-0. Epub 2015 Jul 7.
DNA polymerase (pol) is a ubiquitous enzyme that synthesizes DNA strands in all living cells. In vitro, DNA pol is used for DNA manipulation, including cloning, PCR, site-directed mutagenesis, sequencing, and several other applications. Family B archaeal DNA pols have been widely used for molecular
PMID 26150245

Requirement of the N-terminal residues of human cytomegalovirus UL112-113 proteins for viral growth and oriLyt-dependent DNA replication.

Kim YE1, Park MY, Kang KJ, Han TH, Lee CH, Ahn JH.
Journal of microbiology (Seoul, Korea).J Microbiol.2015 Aug;53(8):561-9. doi: 10.1007/s12275-015-5301-3. Epub 2015 Jul 31.
The UL112-113 region of the human cytomegalovirus (HCMV) genome encodes four phosphoproteins of 34, 43, 50, and 84 kDa that promote viral DNA replication. Co-transfection assays have demonstrated that self-interaction of these proteins via the shared N-termini is necessary for their intranuclear dis
PMID 26224459

Early nucleosome deposition on, and replication of, HSV DNA requires cell factor PCNA.

Sanders I1, Boyer M, Fraser NW.
Journal of neurovirology.J Neurovirol.2015 Aug;21(4):358-69. doi: 10.1007/s13365-015-0321-7. Epub 2015 Feb 12.
Herpes simplex virus (HSV) is a double-stranded DNA virus that can cause lytic infections in epithelial cells of the skin and latent infections in neuronal cells of the peripheral nervous system. After virion attachment to the cell membrane, the capsid enters the cytoplasm and is transported to the
PMID 25672886

Japanese Journal

The common ancestral core of vertebrate and fungal telomerase RNAs

Qi Xiaodong,Li Yang,Honda Shinji,Hoffmann Steve,Marz Manja,Mosig Axel,Podlevsky Joshua D.,Stadler Peter F.,Selker Eric U.,Chen Julian J.-L.
Nucleic Acids Research 41, 450-462, 2013-01
… crassa telomerase synthesizes TTAGGG repeatswith high processivity, a common attribute of vertebratetelomerase. …
NAID 120005323239

Detailed characterization of chitosans, with special relevance to their use as substrates for chitinases

VARUM Kjell M.
キチン・キトサン研究 = Chitin and chitosan research 18(1), 43-46, 2012-04-01
NAID 10030780424

DNAクランプ/複製DNAポリメラーゼ複合体におけるDNA合成・修正スイッチング機構

西田洋一,真柳浩太,石野良純 [他],森川耿右
日本結晶学会誌 52(4), 201-207, 2010-08-31
… Proliferating cell nuclear antigen (PCNA) is responsible for the processivity of DNA polymerase. …
NAID 10026599264