🚀 go-pugleaf

Ken Muldrew (kmuldrew@acs.ucalgary.ca) wrote:
: toms@kaylor.ncifcrf.gov (Tom Schneider) wrote:
: >Ken Muldrew (kmuldrew@acs.ucalgary.ca) wrote:

: >In the famous little book:

: >@book{Schroedinger1947,
: >author = "E. Schroedinger",
: >title = "What is life? the physical aspect of the living cell
: >\& Mind and matter.",
: >publisher = "Cambridge University Press",
: >address = "Cambridge",
: >year = "1947"}

: >I seem to recall that Schroedinger did some calculations about the target size
: >of DNA for radiation.  The point is that you can't "hide" because if you
: >increase the total genomic size, the important genes are still going to be hit
: >at the same rate because they still present the same physical cross section to
: >radiation.  Also, the polymerase won't make fewer mistakes in one place just
: >because it (or an entirely different molecule) also has to function at another,
: >as this may be mostly from thermal noise, which is [everywhere].  Further,
: >increasing the size increases the likelyhood of generating binding sites that
: >sop up proteins from where they are needed.  (The system can eventually evolve
: >to get rid of many if not most, but the probability of them coming up randomly
: >is increased.)  Finally, increased size increases the likelyhood of damage to
: >the long fragile molecule.

: OK, the coding region presents the same cross-section, no doubt about
: that. I had an uneasy feeling when I was typing in that bit. I think
: that what you typed here supports the idea that this DNA isn't simply
: "junk"--a lot of energy goes into taking care of these long, fragile
: molecules.

So the mystery intensifies!  What is the function of the non-coding regions?

: Just to give people an idea of how fragile DNA can be, a
: [Caucasian] without sunscreen, standing in the noon-day sun of the
: tropics, will suffer about 50 000 single strand breaks in every skin
: cell that's exposed per hour (just about the maximal rate of repair,
: coincidence?).

Fascinating!

Perhaps you have references you can share with us for both numbers?

: Another purpose for introns may be to signal the DNA repair or
: proof-reading enzymes to stop. I think that point mutations have
: accrued in the hypervariable regions of immunoglobulin genes at a rate
: that is higher than the replication error rate, implying that there is
: a mechanism to promote mutation. If there was a sequence which told
: the proof-reading enzymes to stop when they reached that particular
: region, then that might be a way of generating the higher mutation
: rate. 

Introns are (presumably!) only on the transcribed RNA copy not the DNA.  One
would generally imagine that repair enzymes do not distinguish the regions,
although Andrez Konopka has shown that the intron and exon have distinct
properties so maybe it is possible.  I'm pretty sure that mutations in
immunoglobulins occur in specific places as part of their rearrangement
mechanism.

: Ken Muldrew
: kmuldrew@acs.ucalgary.ca

  Tom Schneider
  National Cancer Institute
  Laboratory of Mathematical Biology
  Frederick, Maryland  21702-1201
  toms@ncifcrf.gov
  http://www-lmmb.ncifcrf.gov/~toms/