Tuesday, March 22, 2011

~*~*DNA Helicase Articles*~*~

DNA Helicase is an enzyme that temporarily separates the two strands of the double helix of DNA so that it can be replicated by other enzymes. This enzyme doesn't catalyze a specific reaction. Instead, it accomplishes its task by hydrolyzing molecules of ATP and subsequently breaking the hydrogen bonds between the base pairs of the nucleotides that make up the DNA molecule. The WRN protein is a specific helicase.

One member of the family of DNA helicases, the WRN protein, has a key role in maintaining genome stability. If the gene sequence for this protein is missing or defective, a condition called Werner syndrome sets in. This disease is characterized by premature aging and a predisposition to cancer development. Some of the symptoms of "early aging" include early onset of type II diabetes mellitus, atherosclerosis, cataracts, skin atrophy, graying and loss of hair, and osteoperosis. We don't yet fully understand exaclty how WRN functions in these cellular processes, but we do know that WRN is involved in homologous recombination, telomere maintenance, DNA repair, and other processes. So if the WRN protein is missing or defective, the process DNA repair is affected, and this could be the reason that cancer predisposition is a symptom of those with Werner syndrome. 1.

It has also been found that DNA helicase has exonuclease activity. Along with hydrolyzing hydrogen bonds between nucleotide base pairs, the helicase can also hydrolyze the bonds that hold nucleotides in the DNA sequence. This is one way that the helicase can assist in DNA repair and get rid of base pairs that don't fit in the sequence or don't belong there. This is the way in which the helicase enzyme is "involved in the response to DNA damage during replication, as well as recombination and transcription processes." Even though this article is a review of the previous one, no significant advances have been made towards understanding what specific cellular processes are involved in expressing the Werner syndrome phenotype. It is expected that further research into this condition and it's underlying causes will give us more information about how the normal process of aging works, and could even elucidate ways in which the normal process can be slowed or reversed. 2.

An interesting experiment was done involving helicase and the WRN protein at the University of Pittsburgh Graduate School of Public Health. Segments of DNA were exposed to  hexavalent chromium (Cr VI), which is an environmental carcinogen that promotes replication stress and DNA polymerase arrest. It was shown through this experiment that human cells that had no WRN protein showed delayed damage to its telomeres (a segment of DNA at the end of a chromosome that stabilizes the chromosome and prevents the chromosomes from fusing together). This is consistent with the cellular roles of WRN protein that are known. So the conclusion we draw from this experiment is that "WRN protects against Cr(VI)-induced telomere loss and downstream chromosome fusions, but does not prevent chromosome fusions that retain telomere sequence at the fusion point." 3.

1 comment:

  1. Good work, Amanda. What does WRN stand for?

    One minor point--for these references, you should also provide the bibliographic info that includes authors, title, journal, year, and pages.