MOLECULAR
GENETICS II
Chargaff's rules
The race to unveil the structure of DNA was
guided by Chargaff's rules. No model
could be taken
seriously if it violated any of these following guidelines.
1. In DNA, the number of pyrimidines equals the number of purines
that
is C + T = A + G
2. A = T
C = G
3. The A/T and C/G ratios varied among
species but were consistent within a species.
The model proposed by Watson and Crick
(read the original article here) obeys these
rules. In fact, in
their paper to Nature, they write "It has not escaped our notice that
the specific
pairing we have postulated immediately suggests a possible copying
mechanism for the
genetic material". It's been called the understatement of the
century.
DNA packaging
DNA in prokaryotes is "naked";
that is, the molecule is free of any associations with
any other type of
molecule. In eukaryotes, the DNA is complexed with
proteins in a
very structured
manner to form discrete units of heredity in the nucleus called
chromosomes. In
growing cells, the DNA/protein complex is more properly termed
"chromatin".
When cells enter a division phase, the material condenses and can be seen
clearly as
chromosomes. These chromosomes can be "picked out" of the cell and
used to
form karyotypes.
DNA
is packaged in a systematic manner to facilitate regulation and expression.
In the
first level of
folding, the DNA molecule is wrapped around a core of eight histone
proteins and
capped with another histone, H1, to form a nucleosome. When the entire
length of the
molecule is wrapped this way, the resulting structure resembles "beads
on a string".
The nucleosomes are then wrapped tightly to form a 30
nm fibre called a
solenoid. The fibres are
packaged into looped domains (third level) and then finally
placed on non-histone protein scaffolds. At metaphase, the duplicated
chromosome has
a width of 500-700
nm. Remember that DNA itself is only 2 nm wide.
Architecture of a chromosome
GREAT SITE (before I forget)
plus
one more
Chromosomes are more easily seen in a
dividing cell. Chemical agents can stop this
process to view
the duplicated metaphase chromosomes or to take them from the cell
for analysis (see karyotype)
. The two chromatids of the duplicated chromosome
are identical
copies of each other. Each chromatid will be passed
onto a daughter cell
when cell division
is completed. They are held together at a restricted region called the
centromere.
The centromere is sandwiched between proteins called kinetochores that
attach to the
spindle fibres. Extending from the centromere are two arms. The short
arm is termed
"p", and the long arm is termed "q".
When geneticists speak of a specific region
on a chromosome, they will use locators
such as 15q11-q13.
This is the region in chromosome 15 that is deleted in the
Prader-Willi syndrome.
The ends of the chromosomes are called telomeres
and have been associated with
limitations on the
numbers of cell divisions (Hayflick limit) and aging.
Generally, to count chromosomes, one should
count centromeres not chromatids.
The concept of ploidy
Ploidy refers to
the number of sets of chromosomes in a given cell or an organism.
Humans have two sets of chromosomes - one
from each parent. That makes our cells
diploid. Our
gametes - sperm and ova - contain one set of chromosomes to be passed
onto our children:
these cells are haploid. The endosperm
in the seeds of angiosperms
contains three
sets and is, therefore, triploid. Bread
wheat is a hexaploid and
strawberries are octoploid.
Ploidy is
symbolized by the letter N. In humans, N=23. This is the number of
chromosomes in one
set. In our body (somatic) cells, 2N = 46.
Cell cycle
http://www.cellsalive.com/cell_cycle.htm
Each cell has a life cycle that is
determined by its function, location, and complexity.
Brain cells last throughout our lifetimes,
never dividing, and never being replaced if
damaged beyond
repair. Many nerve cells behave this way as well. Much research is
being done to coax
these cells (especially spinal cord nerve cells) to divide and repair.
Cells alternate between periods of growth
and work (interphase) and cell division.
Interphase is the
longest period of the cell cycle and can be broken into three stages.
The G1 phase is the phase when the cell
grows and fulfills its function. It is followed by
the S phase in
which the genetic material is duplicated (think "S" for DNA
synthesis).
In the final phase, the G2 phase, the cell
completes its preparations for cell division.
These stages are identical whether the cell
is destined to undergo mitosis or meiosis.
Cells that are not destined to divide again
are said to be in a G0 phase.
After the G2 phase, the cell will undergo a
division phase: mitosis or meiosis.
Mitosis creates two identical daughter
cells and maintains the ploidy. Any eukaryotic
cell regardless of
ploidy or numbers of chromosomes is capable of
mitotic division.
Mitotic division describes the division of
the nucleus. Many times, but not always,
mitosis is
followed by cytokinesis, which is the division of the
cytoplasm and its
constituents.