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Once more... cloning of a 13 kb fragment into pBR322 - (Mar/07/2006 )

Hi everybody.

Since some weeks I am really trying to clone a 13 kb fragment into pBR322.
I do a sequential digestion with the 13 kb fragment. Nhe I and Sal I. After digestion, I checked the results and the purify the 13 kb fragment with the QiaEx II Kit. The problem is, that the recovery is not that much and i used to ligate it many times, with different rations ( Insert : Vector --> 3:1 ; 6:1, 8:1 , 1:3 , 1:1) and i used to try different cells like TOP10 F' , Stbl4, DH5alpha in transformation.
I doubt, that ligation works because there is no visible band at the size of the expected vector.
I also electroporated the cells but with a negative result. Does anyone has some good tips for further ligation and transformation? Thanks a lot in advance for any given suggestion.

-Fedex-

some where along the line you're losing you 13kb fragment. You might consider increasing the amount of DNA in your digest or trouble shooting your gel extraction. If you digest a larger amount of dna it should increase your recovery accordingly.

-vasussci-

Hi there,

please read this post in reagrds to your DNA. The longer your DNA the more likely DNA damage is if you use EtBr.

http://www.protocol-online.org/forums/inde...showtopic=14056


LeserattePD

QUOTE (Fedex @ Mar 7 2006, 10:58 AM)
Hi everybody.

Since some weeks I am really trying to clone a 13 kb fragment into pBR322.
I do a sequential digestion with the 13 kb fragment. Nhe I and Sal I. After digestion, I checked the results and the purify the 13 kb fragment with the QiaEx II Kit. The problem is, that the recovery is not that much and i used to ligate it many times, with different rations ( Insert : Vector --> 3:1 ; 6:1, 8:1 , 1:3 , 1:1) and i used to try different cells like TOP10 F' , Stbl4, DH5alpha in transformation.
I doubt, that ligation works because there is no visible band at the size of the expected vector.
I also electroporated the cells but with a negative result. Does anyone has some good tips for further ligation and transformation? Thanks a lot in advance for any given suggestion.

-LeserattePD-