User:WeepingBritney/DNA repair prof review

Useful information can be obtained here. Used exclusively, they blur the boundaries between science and “copying out of the dictionary”, our favorite form of “research” in elementary school. Supplemented with peer-reviewed review articles, students can profit. Referencing is spotty, contributing to overall lack of clarity of what is well established and what is speculation. Figures (where from?) are generally appropriate; likely lifted from original sources. Most basics are covered for the two areas.

I think that these sites demonstrate that you get what you pay for. They contain many statements that are “true” according to my reading of the literature, as well as quite a few logical but unsupported claims, and some wackiness. I note some of the raised eyebrows below:


 * Failure to correct molecular lesions in cells that form gametes can introduce mutations into the genomes of the offspring and thus influence the rate of evolution.

''An example of a reasonable but overgeneral claim. Certainly RT error rates contribute to the genomic dynamics of HIV, and background mutation rates are important, but I doubt that a general link between evolution and error rates has been documented.''


 * The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states:
 * 1) an irreversible state of dormancy, known as senescence
 * 2) cell suicide, also known as apoptosis or programmed cell death
 * 3) unregulated cell division, which can lead to the formation of a tumor that is cancerous.

Claims to cover the gamut of possibilities, but what about microbes?


 * The vast majority of DNA damage affects the primary structure of the double helix; that is, the bases themselves are chemically modified

''Poor writing- “that is” seems to indicate that the bases are the primary structure. Also, do we know that the vast majority of damage affects bases, and not the backbone? Who has determined this, and how?''

...exogenous damage caused by external agents such as
 * 1) ultraviolet [UV 200-300nm] radiation from the sun
 * 2) other radiation frequencies, including x-rays and gamma rays
 * 3) hydrolysis or thermal disruption
 * 4) certain plant toxins
 * 5) human-made mutagenic chemicals, especially aromatic compounds that act as DNA intercalating agents
 * 6) cancer chemotherapy and radiotherapy''

''What about alpha radiation, which represents the largest proportion of radiation exposure for the US population in general? (radon)''


 * Thermal disruption at elevated temperature increases the rate of depurination (loss of purine bases from the DNA backbone) and single strand breaks. For example, hydrolytic depurination is seen in the thermophilic bacteria, which grow in hot springs at 85-250°C.[3] The rate of depurination (300 purine residues per genome per generation) is too high in these species to be repaired by normal repair machinery, hence a possibility of an adaptive response cannot be ruled out.

''How do we know this? Sounds like a paragraph lifted from someone’s Discussion.''


 * Whenever a cell needs to express the genetic information encoded in its nDNA the required chromosomal region is unravelled, genes located therein are expressed, and then the region is condensed back to its resting conformation.

''An attractive but generally unsupported assertion. Chromatin changes certainly accompany gene activation/deactivation, but “condensation” certainly would not describe many instances of genes in a quiescent, but “poised” state.''


 * Without access to a template, cells use an error-prone recovery mechanism known as translesion synthesis as a last resort.

''Is this actually known to be true, or is it a guess? How were “last resorts” measured?''

Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing - most typically cancer cells - are preferentially affected. The side effect is that other non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected. Modern cancer treatments attempt to localize the DNA damage to cells and tissues only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body).
 * Inherited mutations that affect DNA repair genes are strongly associated with high cancer risks in humans. Hereditary nonpolyposis colorectal cancer (HNPCC) is strongly associated with specific mutations in the DNA mismatch repair pathway. BRCA1 and BRCA2, two famous mutations conferring a hugely increased risk of breast cancer on carriers, are both associated with a large number of DNA repair pathways, especially NHEJ and homologous recombination.

This section is so short as to be virtually worthless.


 * The fossil record indicates that single celled life began to proliferate on the planet at some point during the Precambrian period, although exactly when recognizably modern life first emerged is unclear.

''Yes, Precambrian is anything before 500 Mya, but good fossil evidence exists that is much older. What the heck does ‘modern life’ mean? Sounds like a conflation of arguments regarding origins of life, the Cambrian explosion and bilaterian evolution.''


 * The rate of evolution in a particular species (or, more narrowly, in a particular gene) is a function of the rate of mutation.

See first comment.