DNA repair

Dr. Sydney Shall sydney.shall at kcl.ac.uk
Fri Dec 15 14:38:14 EST 2000

Evelyn Wright wrote:

> I have two questions to the NG:
> 1. Is the result of Bielas and Heddle, PNAS 97:11391-11396 (October 10
> 2000), namely that DNA replication is necessary for repair, a general
> result, or does it (for some reason?) apply only to their transgenic
> mouse cells? It seems like the latter, since otherwise our non
> proliferating cells would be out of comission after some time shorter
> than the average life span(?).

The result is not strictly correct.  As you surmise non dividing cells
certainly are able to use a number of DNA repair pathways.  However, the
rate of DNA repair is much slower in non dividing cells, than in
replicating cells.  This however, is not a problem because non dividing
cells have a lot of time to execute the repair.  The bulk of bad
consequences resulting from DNA damage occurs during either DNA replication
or during mitosis, that is only in dividing cells.  As you surmise, if non
dividing cells could not do DNA repair, what would our neuronal DNA look
like after 50 or 100 years?

> 2. Are there any studies of how the nuclear genes coding for mtDNA
> repair enzymes are themselves repaired? One can imagine a stable system
> (biological or cybernetic) in which all repair mechanisms can also
> repair each other (it's stable because it would take SIMULTANEOUS damage
> to all repair mechanisms to destabilize it, which is unlikely), but if
> the nodes of this system are not all connected  to each other (i.e.
> repairing each other) and there is an achiles heel node that is least
> connected, the system would become unstable over time and might exhibit
> some of the characteristics of ageing. Is pol gamma the only repair
> enzyme for mtDNA? Does the nuc gene encoding it get repaired by anything

> else?

This is an interesting point.  Clearly the GENES coding for the repair
proteins are repaired by these proteins.  This is OK, however because they
can stop making proteins temporarily with safety


Sydney Shall

> -Iuval Clejan

-- Dr. Sydney Shall, Department of Molecular Medicine, King's College
School of Medicine & Dentistry, The Rayne Institute, 123 Coldharbour Lane,
LONDON, SE5 9NU, TEL: 01 71 346 3126; FAX: 01 71 733 3877, E-Mail:
sydney.shall at kcl.ac.uk


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