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DNA Helicase

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Contents

DNA Helicase

DNA Helicase is a complex, 14 chain structure that unwinds DNA in replication by cleaving the hydrogen bonds between the complementary nucleotides at the replication fork. It is present in both prokaryotes and eukaryotes.

Function

By cleaving the hydrogen bonds between the complementary nucleotides at the , Helicase allows DNA polymerase to access each DNA strand in replication. Aside from its part in DNA replication, it also functions to unwind DNA in repair, transcription, and recombination.

Diseases & Disorders

Malfunctioning helicase causes issues in each of its functions. In general, a malfunctioning helicase affects transcription. The helicase causes missense and nonsense substitutions, frameshift, and deletion mutations. Without helicase, the DNA helix remains locked with hydrogen bonds and DNA polymerase does not have access to either strand.

Cancer and Premature Aging

Helicase separates the two strands of DNA so other enzymes can repair the molecule. If helicase malfunctions and enzymes can't access and repair DNA, the genome may be replicated incorrectly and transcribed in differently folded proteins. Therefore, the cell overall will be affected, which can lead to the unchecked division indicative of cancer.

Human helicase deficient disorders show evidence of this. People afflicted with a deficiency of helicase have a high risk of developing cancer at a young age.

Helicases in Viral Replication

Some strand of viruses will introduce their own helicases to the host which are crucial to the virus' replication. So some new antiviral therapies target viral helicases to shutdown viral replication.

Structural highlights

There are several ligands that bind the various chains together in order to create Helicase. In various places throughout Helicase, a acts as a ligand. Although DNA Helicase is driven by ATP hydrolization, Guanosine-6-Diphosphate, or GDP has a stimulatory effect on DNA Helicase action when used in tandem with ATP. 2-(N-morpholino)ethanesulfonic acid, or is used as a buffer and a ligand in the DNA Helicase complex.

References

  1. https://www.ncbi.nlm.nih.gov/pubmed/11701636
  2. http://www.jbc.org/content/281/27/18265.full
  3. https://academic.oup.com/hmg/article/10/7/741/558547/DNA-helicase-deficiencies-associated-with-cancer
  4. https://www.ncbi.nlm.nih.gov/pubmed/12202752
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