An Important New Study Impacting Our Understanding of DNA Repair
Analysis Reveals Extent of DNA Repair Army is an article of the Howard Hughes Medical Institute which highlights the importance of genomic repair mechanisms; an important theme of this blog. The article, which notes a new study and its related publication in the journal Science, reveals some surprising findings noted by the study's senior author Stephen J. Elledge of Harvard. Quotes from the article in green:
"But precisely how cells monitor the integrity of their genomes, identify problems, and intervene to repair broken or miscoded DNA has been one of nature's closely held secrets. Now, however, a report in the journal Science describes a new database developed by a team of researchers from the Howard Hughes Medical Institute at Harvard Medical School that is providing the first detailed portrait of the army of more than 700 proteins that helps maintain DNA's integrity."
700 proteins involved in maintaining genomic integrity! The essential nature of the function is underlined by the sheer number of proteins involved. More from the article:
"The DNA damage response is a routine event in the life of any cell. Stress caused by environmental factors such as exposure to ultraviolet light, ionizing radiation or other environmental phenomena can cause DNA to break apart or rearrange its nucleotide base pairs in unhealthy ways. If such mutations are left unchecked, they can accumulate over time and lead, ultimately, to cancer or diabetes."
Note the consequences of unrepaired damage to DNA. It is actually more severe than indicated here. Damaged genomes produce defective proteins and impaired regulatory functions.
"Elledge explained that two critical enzymes, known in scientific shorthand as ATM and ATR, act like sensors to detect trouble and initiate the DNA damage response by engaging the cell's molecular repair apparatus."
Before an effective response to a problem can be mounted there must be a recognition that the problem exists. The essential nature of individual proteins is indicated by their functions.
"The results of this study illustrate the extraordinarily broad landscape of the DNA damage response, which extends far beyond what was anticipated from previous studies," he said."
Another indication of the importance of DNA repair. It clearly impacts medicine and should do the same with respect to theories about the origin and diversification of life.
"The proteins, known as Abraxas and RAP80, bind to the BRCA1 protein and form a complex that governs three essential modes of DNA damage control: damage resistance, genetic checkpoints that constrain cell proliferation, and DNA repair. There are three variants of this BRCA1 complex and one is mediated by Abraxas and RAP80, providing potentially different windows into the protective nature of the gene.
“We have to stop thinking about BRCA1 as a single entity. There are three complexes and which complex is doing what? That's what needs to get figured out,” Elledge said.
He noted that simply knowing that BRCA1 comes in three distinct flavors gives researchers the chance to sort out the role of each in the DNA damage response and the onset of tumors."
A pattern that is well entrenched in the history of research. Increasing knowledge is associated with the discovery of ever increasing biological complexity. Three varieties of BRCA1 correspond to three types of damage control: damage resistance, constraining cell proliferation by means of genetic checkpoints and DNA repair. This appears to be a sub-system in which all parts are needed to maintain effective genomic repair.
These are exciting research findings which alter our conception of just how vast and intricate is the network of proteins involved in containing DNA damage, as Elledge so aptly pointed out.
Labels: DNA Repair