discover that a special group of genes functioning within the body's
normal DNA repair process are the main reason for the effectiveness of
p53, the most important gene in preventing human cancer
findings could help doctors better identify patients who have an increased
risk of developing certain cancers and help companies develop safer, more
effective treatments for patients
For the very first
time, a study has explained how the
tumor suppressor gene, p53 is able to prevent cancer growth
. Dr Ana Janic,
Associate Professor Marco Herold and Professor Andreas Strasser from the Walter
and Eliza Hall Institute who led the study have revealed that a special group of genes that function
within the body's normal DNA repair process were vital to the effectiveness of
The findings are
published in Nature
‘Melbourne scientists have discovered the science behind how the most important gene in preventing human cancer, p53, is able to stop the development of lymphoma and potentially other types of cancer.’
"In an exciting
and unprecedented finding, we discovered that the DNA repair gene MLH1and
additional DNA repair genes are critical to p53's ability to prevent the
development of B-cell lymphomas," Dr Janic said.
What is MLH1?
The MLH1 gene codes for the MutL homolog
1, colon cancer, nonpolyposis type 2 (E. coli) protein
. It is a gene commonly associated with a genetic
condition called hereditary nonpolyposis colorectal cancer
that is associated with a high
risk of colon cancer and other cancers.
DNA mismatch repair (MMR) is a system
consisting of seven proteins that recognize and initiate repair of DNA base
; mismatches can arise
during DNA replication and recombination. One
of the components in the MMR system is the MLH1 protein
Research has found
that a defect in the repair mechanism (which is found in about 13% of
colorectal cancers) is due to the deficiency of MLH1 than deficiencies of other
In the current study,
after screening more than 300 downstream targets of p53, the scientists discovered that the loss of the DNA repair gene MLH1
prevented the tumor suppressor gene, p53 from functioning properly, thus
causing the development of lymphoma
. Tumor development was significantly
stalled when MLH1 was put back into the equation.
The p53 gene codes for a protein with the same name that
plays a pivotal role in the body's natural defense mechanism against cancer and
the suppression of tumor formation.
Malfunctioning of the
p53 protein is responsible for half of all cancers in the world. Although being
aware of the significance of p53, researchers have not been able to explain how
the protein is able to block cancer development until now.
The revelation that MLH1 is a powerful weapon for p53 in the fight
against cancer could help doctors diagnose patients earlier and prescribe
safer, more targeted treatments for their cancer.
The scientists also
explored other DNA repair genes to find just how important the whole DNA repair
mechanism is to p53's ability to prevent cancer development.
"Now that we
understand the significance of MLH1 and other DNA repair factors, we can begin
to find ways of identifying the vulnerabilities that their loss may impose on
cancer cells with the aim of exploiting these for therapeutic benefit," Dr
The next steps will
focus on understanding if the DNA repair process has the same cancer-blocking
impact on cancers other than lymphoma, such as pancreatic and colon cancers.
"p53 is mutated
in close to 70 percent of colon and pancreatic
this discovery could have a significant impact on understanding these diseases.
We are therefore keen to test whether genes involved in the DNA repair process
might also play a role in helping p53 prevent the development of these
cancers," she said.
Tumor suppressor gene -
a gene that codes for a protein known as a tumor
that is found in the nucleus
of all cells in the body that helps regulate normal cell growth and
multiplication. Another key function of the p53 protein is the critical role it
plays in suppressing tumors by inhibiting the division and growth of cells
consisting of damaged DNA.
missing or a damaged p53 gene is the cause of over half of all cancers
improper functioning of the p53 gene is responsible for cancer's aggressiveness
,response to treatment and its
ability to spread to other sites in the body. p53 is a key target for the development of therapy against cancer
- p53 Gene - (http://www.whatisbiotechnology.org/index.php/science/summary/p53-gene)