Tuesday, August 08, 2006

Limiting Damage to DNA

In an article entitled 'Researchers identify gene as protector of DNA, enemy of tumors' a single gene is the target of focus. The article is italicized. My remarks are not.

Houston -- A single gene plays a pivotal role launching two DNA damage detection and repair pathways in the human genome, suggesting that it functions as a previously unidentified tumor suppressor gene, researchers at The University of Texas M. D. Anderson Cancer Center report in Cancer Cell.

The advance online publication also reports that the gene - called BRIT1 - is under-expressed in human ovarian, breast and prostate cancer cell lines.



This underscores the necessity to explain the evolution of both a gene of interest and all other genes required to enable its regulation and expression.


Defects in BRIT1 seem to be a key pathological alteration in cancer initiation and progression, the authors note, and further understanding of its function may contribute to novel, therapeutic approaches to cancer.

"Disruption of BRIT1 function abolishes DNA damage responses and leads to genomic instability," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in the Department of Molecular Therapeutics at M. D. Anderson. Genomic instability fuels the initiation, growth and spread of cancer.

A signaling network of molecular checkpoint pathways protects the human genome by detecting DNA damage, initiating repair and halting division of the damaged cell so that it does not replicate.



Indeed. Evolutionists cite natural selection as a directional force responsible for sifting beneficial mutations and preserving them. The existence of a complex of genes needed to detect and repair inevitable damage to DNA is essential to preserve existing functions. This raises the question of how any organism could survive genomic corruption prior to a putative point in time when no such damage limiting mechanisms existed.


In a series of laboratory experiments, Lin and colleagues show that BRIT1 activates two of these checkpoint pathways. The ATM pathway springs into action in response to damage caused by ionizing radiation. The ATR pathway responds to DNA damage caused by ultraviolet radiation.


Note that causes of genomic damage would be present at a point in time when the first life forms appeared. It is not a matter of confronting a challenge presented only to more advanced forms of life.


By using small interfering RNA (siRNA) to silence the BRIT1 gene, the scientists shut down both checkpoint pathways in cells exposed to either type of radiation.

Researchers then used siRNA to silence the gene in normal human mammary epithelial cells (HMEC). The result: Inactivation of the gene caused chromosomal aberrations in 21.2 to 25.6 percent of cells. Control group HMEC had no cells with chromosomal aberrations. In cells with the gene silenced that were then exposed to ionizing radiation, 80 percent of cells had chromosomal aberrations.



Genetic disaster ensues when DNA detection and repair mechanisms are disabled.


"We also found that BRIT1 expression is aberrant in several forms of human cancer," Lin said. The team found reduced expression of the gene in 35 of 87 cases of advanced epithelial ovarian cancer. They also found reduced expression in breast and prostate cancer tissue compared with non-cancerous cells.

Genetic analysis of breast cancer specimens revealed a truncated, dysfunctional version of the BRIT1 protein in one sample.

Loss of the DNA damage checkpoint function and the ability to proliferate indefinitely are two cellular changes required for the development of cancer. Lin and colleagues have now tied the gene to both factors. They previously identified BRIT1 as a repressor of hTERT, a protein that when reactivated immortalizes cells, allowing them to multiply indefinitely.



Cells have multiple interacting components as this one gene illustrates. The necessity of functional regulators is aptly portrayed by the article.

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