Tuesday, April 26, 2011

Why DNA Helicase is Protein Of The Year!

Many different forms of DNA Helicase exist in the world, with slight differences in structure generally occurring between species of living organisms (shown below). Most of the crystal structures of helicases that have been solved so far have come from small bacteria or yeast, where it's easiest to isolate the one specific enzyme. But despite these different forms and structures, all forms of DNA Helicase have the same, very important job. It uses the energy from hydrolysis of ATP to break the many hydrogen bonds that form between base pairs of the nucleic acids that make up DNA and keep it held together in its classic double-helical shape.
  1CR1            1Q57
                                 Bacteriophage T7 DNA helicase crystal structures

The products of the "reaction" then are single strands of DNA that have been unzipped and can then be replicated by other enzymes.

We never really give much thought to how much work our proteins do inside our bodies, and rarely do we recognize them at all unless something goes wrong. But when we think about DNA helicase, this one tiny protein that is an integral part of all living organisms, it's an incredible thought. This enzyme has been working since the very moment our cells began replicating, and without it, we wouldn't have made it past one cell! Not one organism on earth would be alive were it not for this motor enzyme moving along the backbone of the nucleic acids that make up our DNA. And even though most DNA replication errors occur later down the line, DNA helicase still has a pretty impressive record for how few mistakes it makes. This protein is essential for multicellular life to happen and be sustained. Be thankful for DNA Helicase!

A proposed mechanism for how DNA helicase works can be seen at http://www.youtube.com/watch?v=UWNhwceMjfk


1. Foadey, Wilfried. DNA Helicase: Function/Role. N.p., 5 Nov. 2004. Web. 26 Apr. 2011 <http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Projects04/HELICASE/FUNCTION.html>.
2. "Helicase." Wikipedia: The Free Encyclopedia. N.p., 28 Mar. 2011. Web. 26 Apr. 2011. <http://en.wikipedia.org/wiki/Helicase>.
3. Lionnet, Timothee, Michelle M. Spiering, Stephen J. Benkovic, David Bensimon, and Vincent Croquette. "Real-time observation of bacteriophage T4 gp41 helicase reveals an unwinding mechanism." Proc Natl Acad Sci USA 104.505 Dec. (2007): 19790-95. Web. 26 Apr. 2011. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2148377/?tool=pmcentrez>.

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.