Some mutagens strip DNA nucleotides bases of essential modifications—for example, they deaminate the bases—such that these bases resemble different nucleotides and confuse the DNA replication machinery. Subsequent rounds of DNA replication then permanently incorporate such changes.
Other mutagens, such as ethidium bromide, a common lab reagent, look so much like base pairs that they intercalate or stick between nucleotides, which can lead to insertion or deletion of an extra base pair following the next round of DNA replication. Radiation is another type of environmental mutagen that may cause direct changes in a cell's DNA.
For instance, ionizing radiation i. Lower-energy radiation, such as UV rays, can also penetrate cellular and nuclear membranes. One way this penetration can damage DNA is by cross-linking chemically gluing two bases together. Cells generally attempt to fix such breaks by a process called homologous recombination , but sometimes this process goes wrong.
For example, when multiple breaks are joined together in the wrong order a phenomenon known as nonhomologous end-joining , the result can be a loss of large, gene-rich regions of DNA. Because accurate repair of such damage is so important, cells have cell cycle checkpoints, or mechanisms designed to stall continued cell division until the DNA can be repaired.
Interestingly, DNA repair pathway genes are often mutated in cancers and other genetic disorders. For instance, xeroderma pigmentosum, a disorder of the skin, is caused by mutations in DNA repair enzyme genes, and these mutations can lead to greatly increased susceptibility to skin cancer.
Genetic deficiencies can also compound susceptibility to breast cancer Ronckers et al. Early evidence that suggested these genes were involved in DNA repair was mostly circumstantial. For instance, the expression levels of these genes correlate with cell division , peaking during the S phase , therefore suggesting a role in replication, which is also when DNA repair occurs Blackshear et al.
Sharan's research team in particular demonstrated that cells lacking a wild-type BRCA2 gene were hypersensitive to DNA damaging agents. The null cells were unable to survive the damage, whereas the normal cells survived, presumably because they retained the capacity to repair radiation-related damage Figure 2.
Specifically, cells that lack a normal BRCA2 gene exhibit up to a hundredfold reduction in the rate of homologous recombination Moynahan et al. Thus, mutations in the BRCA genes have been proposed to allow misregulation of DNA repair possibly leading to tumorigenesis, although other mechanisms have also been proposed. Changes in DNA caused by mutagens can have a range of effects, depending on where these changes happen to occur within the genome.
Some mutations are silent, exerting no effect upon the amount or quality of the protein made from a given gene. Other mutations can be more severe, and they may even lead to complete loss of protein production. Fortunately, humans have two active copies of most genes, which provides some protection against the deleterious effects of mutation.
However, this is not always the case. For instance, males have only one copy of the genes carried on the X chromosome , and an entire copy of this chromosome is silenced in females. Moreover, gene-gene interactions, or epistasis , can amplify the consequences of partial loss of a single gene.
That is, if multiple genes are required for a particular process, damage to even a single copy of one of those genes can damage the entire pathway.
The role of gene interactions in the etiology of human disease is therefore a critical area of study. Blackshear, P. Oncogene 16 , 61—68 Connor, F. Nature Genetics 17 , — link to article. Kessin, R. Cell motility: Making streams. Nature , — link to article. Konijn, T. Identification of adenosine-3', 5'-monophosphate as the bacterial attractant for myxamoebae of Dictyostelium discoideum.
Journal of Bacteriology 99 , — Moynahan, M. BRCA2 is required for homology-directed repair of chromosomal breaks. Molecular Cell 7 , — Powell, S. Oncogene 22 , — Ronckers, C.
Radiation and breast cancer: A review of current evidence. Breast Cancer Research 7 , 21—32 Scully, R. Cell 88 , — Sharan, S. Wong, A. Journal of Biological Chemistry , — Xu, X. Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells.
Molecular Cell 3 , — Atavism: Embryology, Development and Evolution. Gene Interaction and Disease. Information about mutagenic effects, if known, will be found in Section 11 toxicological information of an SDS. However, very few chemicals have ever been tested for mutagenicity, so the absence of information in this section does not necessarily mean that substance is not a mutagen!
If the Safety Data Sheet indicates the material is a mutagen you should consider substituting it with a less hazardous material. Safety Emporium has all kinds of lab equipment such as rotary evaporators. See also : carcinogen , clastogen , cytotoxin , teratogen.
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