Navigation Links
DNA size a crucial factor in genetic mutations, study finds

Researchers at Stanford University have created a larger-than-normal DNA molecule that is copied almost as efficiently as natural DNA. The findings, reported in the Oct. 25 online edition of the Proceedings of the National Academy of Sciences (PNAS), may reveal new insights into how genetic mutations-tiny mistakes that occur during DNA replication-arise. The discovery was made in the laboratory of Eric Kool, a professor of chemistry at Stanford and co-author of the PNAS study.

DNA, the genetic encoder of life, comes in two parallel strands that form a double helix. It's like a long, twisted ladder where each rung consists of two molecules that form a base pair. DNA has four bases: adenosine (A), thymine (T), guanine (G) and cytosine (C). A always pairs with T, and G with C. To copy itself, the DNA molecule unwinds and splits. Either strand is now a template to build a new DNA molecule. An enzyme-a protein that speeds the reaction, in this case the bacteria E. coli's DNA polymerase I-moves along the template and selects the corresponding base to create a new base pair.

DNA bases fit into a specialized site on the enzyme before they are bonded to the template. Kool wanted to see how the enzyme reacts if the bases are not the usual size. ''The idea was to see how DNA replication depends on size,'' Kool says.

The researchers investigated it by offering bases of different sizes to the DNA polymerase I enzyme and measuring how accurately the enzyme made new DNA copies. About once every 10,000 to 100,000 times the enzyme will put in the wrong base, choosing for instance a G instead of a T to pair with an A. The rate that the enzyme accurately copies DNA is known as its efficiency.

These rare and random mistakes can cause genetic mutations. While we tend to heap negative connotations onto the term, some mutations create new traits that actually benefit the organism or yield no effect. These small-scale changes, collectively called genetic drif t, play an important role in evolution, as does natural selection.

To make their DNA bases, Kool started with a molecule similar to thymine-called an analog-and made five different sizes by adding increasingly larger atoms. The first analog was smaller than natural thymine, the second about the same size and the last three were increasingly larger. The difference between the smallest and largest analogs was only one angstrom, or a tenth of a nanometer.

Bigger is better

When the researchers offered the analog bases to DNA polymerase I, the enzyme not only recognized the synthetic molecules as it would natural DNA but also copied one of the slightly larger analogs at a rate 22 times more efficiently than the natural-sized analog. In fact, DNA polymerase I incorporated the slightly larger analog almost as efficiently as it did natural thymine, both in the test tube and in live E. coli bacteria. In contrast to this, the smallest and largest analogs in the set were rejected by the enzyme and the bacteria.

According to Kool, these results indicate that size is a strong factor determining enzyme efficiency-and a mechanism for allowing mutations into the DNA molecule.

''It's a way the organism can evolve,'' Kool says. ''If the protein that copies DNA prefers a molecule that's slightly bigger than natural DNA, then it can accept mistakes more readily.'' For example, although T is supposed to match up with A, it might be inclined to pair with G, which has a slightly larger configuration.

The sheer fact that a living system readily used a base-or nucleotide-that was artificially created is itself groundbreaking. ''Here we have, I think, the first example of an efficient, human-designed nucleotide working in a live cell,'' he says.

Kool and the gang are now exploring ''the funny finding that the bugs prefer DNA that's larger than natural DNA'' by making larger nucleotides. ''Size and shape are related issues, so we 're interested now in keeping the size constant and changing the shape,'' Kool adds.


'"/>

Source:Stanford University


Related biology news :

1. Epstein-Barr virus protein crucial to its role in blood cancers
2. Researchers identify protein crucial for survival of Lyme-disease bacterium
3. Molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves
4. Scientists discover the bodys marijuana-like compounds are crucial for stress-induced pain relief
5. Einstein scientists discover how protein crucial for motion is synthesised at the right place in the cell
6. Source of crucial immune cell in the skin discovered
7. Researchers add crucial information on how the bodys T cells react to parasitic diseases
8. Heart has enough oxygen to survive hypothermia, CPR crucial
9. Scientists identify protein with a crucial role in cell death
10. Neural stem cell gene plays crucial role in eye development
11. Brown team finds crucial protein role in deadly prion spread
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/19/2016)... 20, 2016 The new GEZE ... compact web-based "all-in-one" system solution for all door components. ... or the door interface with integration authorization management system, ... systems. The minimal dimensions of the access control and ... building installations offer considerable freedom of design with regard ...
(Date:3/31/2016)... Florida , March 31, 2016 ... ) ("LegacyXChange" or the "Company") LegacyXChange ... potential users of its soon to be launched online ... ( https://www.youtube.com/channel/UCyTLBzmZogV1y2D6bDkBX5g ) will also provide potential ... use of DNA technology to an industry that is ...
(Date:3/22/2016)... PROVO and SANDY, Utah ... Ontario (NSO), which operates the highest sample volume laboratory ... and Tute Genomics and UNIConnect, leaders in clinical sequencing ... announced the launch of a project to establish the ... panel. NSO has been contracted by ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... ... May 25, 2016 , ... Scientists at the University of ... tried for mesothelioma may be hampering the research that could lead to one good ... here to read it now. , The team evaluated 98 mesothelioma patients ...
(Date:5/24/2016)... Israel , May 24, 2016   MedyMatch Technology ... physicians with artificial intelligence, real-time decision support tools in the ... present at the 2016 Israeli Advanced Technology Industries (IATI) BioMed ... Israel,s 15th National Life Sciences and ... at the David Intercontinental Hotel in Tel Aviv, ...
(Date:5/23/2016)... 2016 Zimmer Biomet Holdings, Inc. (NYSE and SIX: ... its Board of Directors has approved the payment of a ... 2016. The cash dividend of $0.24 per ... to stockholders of record as of the close of business ... to approval of the Board of Directors and may be ...
(Date:5/22/2016)... (PRWEB) , ... May 22, 2016 , ... Doctors in ... in combating the asbestos cancer, malignant mesothelioma. Surviving Mesothelioma has just posted an article ... in the University of Rome’s Department of Clinical Sciences and Translational Medicine evaluated more ...
Breaking Biology Technology: