DNA replicase

[Giles]

It's a long shot, but does anyone know whether knocking out the associated mismatch-repair exonuclease (so it is present but non-functional) stops DNA synthesis by the main DNA replicase in its tracks when a mismatch occurs, or just slows down synthesis?

 

I know the answer might differ for the various types, but i think i can cope with the shock...

 

(I ask because the normally excellent MBoC seems to contradict itself on this : / )

[fafalone]

I'd reason that it just slows it down, just because very rarely will one protein be completely responsible for a function taking place... but I don't think an organism with the gene knocked out would develop.

[daisy]

Hmm...guess someone will just have to do the experiment eh? It probably would (my guess too) just create hiccups but the hiccups might accumulate pretty fast and apoptosis could set in pretty quickly? I really have no idea...interesting question....old Alberts et al. is confused on the issue?.......you've prompted me to go off and refresh my memory. Seeing a grant proposal in there somewhere Glider? (haha).

[Giles]

normally you would probably be right faf, but the polymerase should require a properly matched pair to synthesise a new chain on the end of (DNA polymerases can't start new chains without a free 3'-OH on the DNA or RNA "primer strand").

 

The problem is that page 249 of alberts et al. (4th ed.) describes an E. coli mutant with a 'defective' proofreading exonuclease, which apparently cause errors to accumulate, which implies synthesis is going on. (p. 242 of the same book makes it pretty clear it shouldn't)

 

i wonder if this particular mutant has some other property too, which allows synthesis to carry on.

[blike]

My biology book has a small bit about errors accumulating as well. "Researchers spotlighted the importance of such proteins[mismatch-repair] when they found that a hereditary defect in one of them that is associated with a form of colon cancer. Apparently, this defect allows cancer-causing errors to accumulate in the DNA."