Re: What is the ratio between nuclear proteins and DNA in a cell?

This is a tough question to answer cleanly, given the widely varying 
composition of cells across species or even considering a comparison of 
differentiated cells from a single type of organism.  For example, as red 
blood cells are matured, the nucleus is ejected (giving the RBC’s their 
characteristic doughnut shape); so in RBC’s, there is neither DNA nor 
nuclear protein.  (This is an extreme case, but illustrates the 
morphological diversity of cells).

Either my textbooks are too old or I just don’t have the right resource to 
provide a “textbook” answer to your question, but we can speak in 
generalities and can learn something from back-of-the envelope 
calculations.  Typical cellular dimensions are 1-5 microns for prokaryotic 
(bacterial) cells and 10-100 microns for eukaryotes, with WIDE variations 
cited for both.  Still, considering these numbers, we can estimate a 
prokaryotes cell’s volume to be in the range of 1-5 picoliters (that’s 
1*10^-12, or one trillionth of a liter), and for eukaryotes, that number 
is on the order of 5 picoliters to 5 nanoliters, a whopping volume on the 
atomic scale.

Normal double-stranded DNA has a predictable topology of 10 base pairs per 
helical turn, with a repeat of 3.4 nanometers per turn and an axial 
diameter of 2 nanometers; this gives us an approximate volume of one cubic 
nanometer per base pair of DNA, or roughly 1*10-24 liter per base pair.  
Considering cells contain <10^6 kilobases of DNA for bacteria, and 
somewhere in the range of 10^7 to 1o^11 kilobases of DNA in eukaryotes, we 
can estimate around 1% of a cell’s volume is comprised of DNA (give or 
take).  The lesson being that MOST of a cell’s volume is made up of other 
things, consistent with the role DNA plays as the information storage 
vehicle of a cell.  That begs the question, if DNA is only a small 
fraction of a cell’s volume (and mass), what is a cell generally made of?

Again, we’re speaking in generalities since cell composition varies so 
widely, but in general cells are made up of lipids/membranes, and 
proteins.  In eukaryotic cells, lipid bilayers make up all the various 
compartments within a cell (such as the nuclear envelope, the endoplasmic 
reticulum, the golgi, the lysozomes, etc.).  In prokaryotic cells, the 
lipid membrane is the only barrier for the poor little bacterium, so its 
membrane is a bramble of proteins and carbohydrates that are embedded in 
the membrane.  These make up a considerable fraction of a cell’s mass (so 
wide, I hate to even give you a number, but it is on the order of 10’s of 
a percent of a cell’s mass).

The interior of a cell is a crowded environment.  While it is mostly made 
up of proteins, everything else a cell makes or needs is floating around 
as ell; all of the sugars needed for metabolism, all of the nucleotides 
and amino acids needed for cellular biosynthesis, the byproducts/waste 
material from metabolism, vitamins/cofactors, etc.  It is much more like a 
very dense, gelatinous goo than it is a thin, dilute solution.  Much of 
the cell is made up of the hundreds of thousands of proteins needed to 
address the daily needs of a cell’s life.

It is important to note that much of our cellular regulatory functions are 
dealt with on the basis of immediate need.  To properly speak to this 
would require a separate lengthy discussion; suffice to say that new 
proteins are made only when they are needed.  It is costly to keep 
proteins on hand that are hanging out, waiting for something to do; not 
only is there not room in a cell for all of the proteins all at once, but 
it’s a waste of energy to make proteins when not needed.  When there is a 
metabolic need, the proper signal is sent to the nucleus signaling new 
mRNA transcription, followed by rapid translation into proteins on the 
ribosomes.  The lifetime of mRNA and of any given protein is relatively 
short (again, varies widely), but in most cases they are recycled 
naturally by enzymatic digestion, reverting back to nucleotides and amino 
acids within minutes to days.  To work well, this process must be fast and 
efficient on the synthesis side; for this reason, the next largest 
fraction of a cell’s composition is generally made up of ribosomal 
proteins and ribosomal RNA.  Ribosomal proteins make up the biggest single 
type of protein in almost any cell (on the order of 2-10% of a cell’s 
mass), while ribosomal RNA (rRNA) is fully 95% of all sources of RNA.  
Likewise, the machinery responsible for processing immature messenger RNA 
within the nucleus comprises a relatively large fraction of the total 
nuclear proteins, given the importance of rapidity in the mRNA maturation 
process.

Carrying on with the theme of transient protein expression, your question 
concerns the fraction of nuclear proteins, thinking that perhaps there may 
be a correlation between DNA damage repair and the mass of proteins around 
able to mediate DNA repair.  Reminding ourselves that prokaryotes lack a 
nucleus, we’re concerned with eukaryotic cells.  Recall that cellular 
replication is a rare event; during most of the lifecycle of the cell, DNA 
is intertwined with histone proteins and is largely inaccessible.  During 
this period, only segments of DNA containing protein-coding regions are 
being read-out by host RNA polymerases, and only rarely.  Though there is 
potential for DNA damage to occur at any time, the proteins responsible 
for DNA damage repair are not actively produced during these long periods 
of time when replication is dormant.  During replication and in the G2 
phase leading up to replication, DNA damage repair enzymes are actively 
produced, but they still do not comprise a large fraction of the total 
protein mass of a cell.

Though I did not give you as quantitative an answer as you likely hoped to 
get, I hope I did provide a little more food for thought.  Thanks for your 
intersting question.

Regards,
Dr. James Kranz