- Pax5 is a protein that compactly packages DNA in
the nucleus of immune cells, like B-cells
- Pax5 can help access the information contained in
the DNA at any time for maintaining adequate cell functionality and
optimal immune health
- Proper functioning of Pax5 can help to guard the immune system against diseases like cancer
Immune health can
be maintained by the highly compacted ordering and packaging of the genetic
material (deoxyribonucleic acid or DNA) in immune cells by a protein called
Pax5, new research suggests. The study has just been published in the journal Nature Immunology
Scientists at the
Walter and Eliza Hall Institute, Victoria, Australia, have shown that a protein
called Pax5 (Paired Box-5)
can package DNA in a highly ordered and tightly bound fashion within the
nucleus of immune cells such as B-cells. This class of immune cells originate
in the bone marrow, hence
giving rise to the name, B-cells. These B-cells require the information encoded
by the DNA for maintaining their normal structure, function and ability to
fight off diseases. If,
however, Pax5 malfunctions, it can lead to diseases like cancer,
the study findings
‘Pax5 is a protein that compactly packages DNA in B-cells. The genetic information encoded by the DNA can be accessed at any time for maintaining adequate cellular functions and immune health. Optimal Pax5 activity is required for prevention of diseases like cancer.’
The Walter and
Eliza Institute research team was headed by Drs. Rhys Allan and Tim Johanson,
in collaboration with Prof. Stephen Nutt, and bioinformatics experts Prof.
Gordon Smyth and Dr. Hannah Coughlan.
Pax5 Keeps DNA Ordered
The study has shown
for the first time, how Pax5 can scan the genome, appropriately fold the DNA
molecules, and neatly package them into the cell nucleus. In this regard,
Johanson indicated that this highly efficient folding and packaging is crucial
since, a single cell contains
approximately two meters of DNA
, which has to fit into a space much lesser than a
grain of sand.
indicated that cells need to regularly access the information contained in
specific regions of the DNA, as and when needed, so that multiple functions can
be carried out for maintaining good immune health. For example, DNA contained
in B-cells possesses information that is used for producing antibodies, which
are the active components of vaccines, which prevent infectious diseases.
Dr. Johanson said:
"Think of how a meticulously ordered suitcase increases your chance of finding
a specific item of clothing at a moment's notice, and, how a jumbled case could
work against you finding what you need. In the case of our bodies, the
difference between order and disorder can be a matter of life and death."
Disordered DNA can Cause Disease
Dr. Allan indicated
that disordered DNA can lead to complications at a later stage in the process
of retrieving information encoded by the DNA molecule. He was of the opinion
that even very minute errors during DNA organization could lead to diseases.
Dr. Allan said: "A
lack of instructions required to function can put cells at risk of morphing or
devolving into something they perhaps shouldn't be - like a cancer cell. It is
therefore unsurprising that Pax5 is faulty in many childhood leukemias
Advances in Bioinformatics
Dr. Hannah Coughlan
indicated that the activity of Pax5 across the genome could be visualized for
the very first time due to major advances in computing technology. She said:
"With the help of powerful computers, we performed thousands of complex
calculations to spot the difference in DNA organization when Pax5 was present,
versus absent, from the B-cells. Our analyses showed that without Pax5, the
cells could no longer package their DNA adequately." She added: "Bioinformatics
is shining a light on how vital factors regulate our DNA. This in turn
progresses an understanding of what could be going wrong in cases of disease."
Dual Function of Pax5
Pax5 has been
classically regarded as a transcription factor, which helps to decode the
information contained in DNA. However, this is the first time that Pax5 has been assigned a dual function.
function is its ability to meticulously organize and package DNA molecules,
which was not known, until now.
Source of Funding
The research study
was funded by grants from the Australian National Health and Medical Research
Council (NHMRC), the Australian Research Council, the Victorian State
Government and the Australian Government's NHMRC Independent Research Institute
Infrastructure Support Scheme.
- Immune health maintained by meticulously ordered DNA - (https://www.wehi.edu.au/news/immune-health-maintained-meticulously-ordered-dna)