Did you precipitate your DNA with isopropanol or EtOH? Which salt did you use? Was the precipitate following an organic extraction (carry over of solvent or protein from organic/aqueous phase separation). My guess is you most likely have overdried the DNA pellet, or have protein contaminant carry over.

After you wash the precipitated pellet with 70% ethanol, pulse spin and pipette off all residual EtOH visible, allow pellet to dry at room temp for about 5-10 min max until DNA just goes translucent, then add TE. A trick: smell the tube before adding TE to make sure all EtOH has evaporated. Let sit in TE on ice and flick occasionally for 1-2h, then keep at 4oC overnight. Mix a lot to homogenize, but viscosity will remain an issue with high Mol Wt DNA. Spec an appropriate dilution of the DNA (use 50nM NaOH as a blank for the Spec). Contaminants will show up at A230 and A280. If you get one of these shoulders in your DNA spectra, you'll know what the problem is (protein, alcolol, organic solvent carry over, etc). Good luck!

Hi, your pellet was most likely overdried. I had a similar problem (sometimes I had a problem to dissolve the pellet) and sometimes heating the solution to almost boiling T may be useful for a short period of time. However, this may damage your sample. Good luck!

Hi, it could be due to too much DNA for the TE volume or the pellet is over-dried as Mr.Thomas has stated. I would suggest heating the DNA sample at 55C or 60C for an 1h instead of 10 minutes after adding more TE.

By the way, do you see a "cloudy" solution after the overnight incubation? and did you use 1X TE buffer? If you do see the "cloud", it could be caused by excess salt. In that case, try running the precipitation step once again and try dissolving the DNA in 1X TE at 40C overnight incubation.

Hope this helps. Good luck :)

There may be more than one problem. First, if the pellet does not go in solution there may be other material there, in addition to DNA. Did you run a UV spectrum to check the purity and concentration of your DNA? Did you cut your DNA from an agarose or acrylamide gel? Second, your solution may come out of the well if your loading dye does not have enough sucrose (or glycerol). You may try to increase the density of your loading buffer by adding more sucrose (up to 30%); your samples should sink nicely in the well.

The DNA concentration seems to be very high that is why you are getting a viscous solution. It sticks to your pipette and actually does not enter the well of agarose gel at at.. Try using a diluted sample after proper dissolution and concentration check by UV spectrum..good luck

thank you all for your suggestions,,,,, but i have a doubt, if keep at 60 degree for long aftr dilution, i will loose my small fragments of DNAs right?(since i wanted to detect the fragmented DNA). Or else can anybody suggest me any other method to detect fragmented DNA?

Hi, incubation at a temperature higher than 45 degree Celsius for an hour will not cause major harm to your DNA since its origin is genomic and you will still be able to run a decent gel and see the fragments. Once again, if you really wish to get a proper result, I would recommend switching to a DNA extraction kit (we use Qiagen kits) that lets you skip the pellet dissolving part since it uses columns to separate DNA.

Did you precipitate your DNA with isopropanol or EtOH? Which salt did you use? Was the precipitate following an organic extraction (carry over of solvent or protein from organic/aqueous phase separation). My guess is you most likely have overdried the DNA pellet, or have protein contaminant carry over.

After you wash the precipitated pellet with 70% ethanol, pulse spin and pipette off all residual EtOH visible, allow pellet to dry at room temp for about 5-10 min max until DNA just goes translucent, then add TE. A trick: smell the tube before adding TE to make sure all EtOH has evaporated. Let sit in TE on ice and flick occasionally for 1-2h, then keep at 4oC overnight. Mix a lot to homogenize, but viscosity will remain an issue with high Mol Wt DNA. Spec an appropriate dilution of the DNA (use 50nM NaOH as a blank for the Spec). Contaminants will show up at A230 and A280. If you get one of these shoulders in your DNA spectra, you'll know what the problem is (protein, alcolol, organic solvent carry over, etc). Good luck!

I agree with Mohammad, suggest even to dilute DNA 10X prior the precipitation!!! Than you aliquot it in ten instead of one tube, than go on as Heather suggest (regard:). Remember, the contaminants co-precipitate with your DNA, when diluted can decrease in the pellet dramatically. Smaller pellets, better ethanol wash, easier to re-suspend. Only disadvantage is ten times more of pipetting ;(

20mM EDTA pH 8 in your TE buffer can help DNA, which loves basic solution, hates magnesium;)

If your sample is free from (protein, alcohol, organic solvent etc) which you can determine from spectral analysis of your samples? The problem of dissolution seems related to overheating of the pellet (So avoid hard dry) and less TE/Water buffer to dissolve with. How are you washing your pellet with 70% Ethanol? Are you resuspending the pellet in it or just washing it unattended? Sometimes proper washing also helps with purity (By reducing contaminants) and finally increases the solubility. Good Luck!!!

The source of the problem is that this is genomic DNA. I am rather disappointed that no one of the answers above knows this. Very large molecules of DNA produce a very viscous solution and that is the source of the problem you describe. It doesn't matter what the procedure was for isolation, precipitation, or if the DNA was heated to bring it back into solution.  Most of the time the isolation procedures such as vortexing of solutions will shear the DNA enough that it doesn't produce a viscous solution but if it is largely intact then the type of viscous, sticky solution you describe is exactly what you get.  For most applications, gentle shearing of the DNA by either passing the solution several times through a 22 or 25 gauge hypodermic needle or very brief sonication will reduce the viscosity and convert the mixture into a solution which can be easily handled. 

I encounter the same issue whenever I isolate genomic DNA from cells. After precipitation, I resuspend my pellet and let it sit for 2 hours at 55 degrees C. This helps, but as was mentioned large amounts of genomic DNA will be a bit viscous.

recently, I also have these problem. the pellets cannot dissolve(even in 65 degrees C 45-60min) .  I use Nanodrop to measure the concentration and all of them up to 4000-5000ng. But when I use agrose gel to check them, nothing.  And the 260/280, 260/230 is fine.