Primase

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DNA primase is an enzyme involved in the replication of DNA. DNA primase is, in fact, a type of RNA polymerase which creates an RNA primer (later this RNA piece is removed by a 5' to 3' exonuclease); next, DNA polymerase uses the RNA primer to replicate ssDNA.

Primase catalyzes the synthesis of a short RNA (or DNA in some organisms [1]) segment called a primer complementary to a ssDNA template. Primase is of key importance in DNA replication because no known DNA polymerases can initiate the synthesis of a DNA strand without an initial RNA or DNA primer (for temporary DNA elongation).

Function[edit]

In bacteria, primase binds to the DNA helicase forming a complex called the primosome. Primase is activated by DNA helicase where it then synthesizes a short RNA primer approximately 11 ±1 nucleotides long, to which new nucleotides can be added by DNA polymerase.

The RNA segments are first synthesized by primase and then elongated by DNA polymerase.[2] Then the DNA polymerase forms a protein complex with two primase subunits to form the alpha DNA Polymerase primase complex. Primase is one of the most error prone and slow polymerases.[2] Primases in organisms such as E. coli, synthesize around 2000 to 3000 primers at the rate of one primer per second.[3] Primase also acts as a halting mechanism to prevent the leading strand from outpacing the lagging strand by halting the progression of the replication fork.[4] The rate determining step in primase is when the first phosphodiester bond is formed with the ssDNA.[2] The crystal structure of primase in E. coli with core that contained the DnaG protein was determined in 2000.[3] The DnaG and primase complex is cashew shaped and contains three subdomains.[3] The central subdomain forms a toprim fold which is made of a mixture five beta sheets and six alpha helices.[3] The toprim fold is used for binding regulators and metals. The primase uses a phosphotransfer domain for the transfer coordination of metals, which makes it distinct from other polymerases.[3] The side subunits contain a NH2 and COOH terminal made of alpha helixes and beta sheets.[3] The NH2 terminal interacts with a zinc binding domain and COOH-terminal region which interacts with DnaB-ID.[3] The replications mechanisms differ between different bacteria and viruses where the primase covalently link to helicase in viruses such as the T7 bacteriophage.[4] In viruses such as herpes simplex virus (HSV-1), primase can form complexes with helicase.[5] The primase-helicase complex is used to unwind dsDNA and synthesizes the lagging strand using RNA primers[5] The majority of primers synthesized by primase are two to three nucleotides long.[5]

Types[edit]

External links[edit]

References[edit]

  1. ^ Bocquier, Arnaud A. (2001). "Archaeal primase". Current biology 11 (6): 452–456. 
  2. ^ a b c Griep, Mark A. (1995). "Primase Structure and Function". Indian Journal of Biochemistry & Biophysics 32 (4): 171–8. PMID 8655184. 
  3. ^ a b c d e f g Keck, James L. , and Daniel D. Roche, A. Simon Lynch, James M. Berger. (2000). "Structure of the RNA Polymerase Domain of E. coli Primase". Science 282 (5462): 2482–6. doi:10.1126/science.287.5462.2482. PMID 10741967. 
  4. ^ a b Lee, Jong-Bong , and Richard K. Hite, Samir M. Hamdan, et al. (2006). "DNA primase acts as a molecular brake in DNA replication". Nature 439 (7076): 621–624. doi:10.1038/nature04317. PMID 16452983. 
  5. ^ a b c Cavanaugh, Nisha A., and Robert D. Kuchta (2009). "Initiation of New DNA Strands by the Herpes Simplex Virus-1 Primase-Helicase Complex and Either Herpes DNA Polymerase or Human DNA Polymerase alpha". J. Biol. Chem. 284 (3): 1523–1532. doi:10.1074/jbc.M805476200. PMC 2615532. PMID 19028696.