DNA is a double stranded helix, constituted by four nucleic bases: adenine, thymidine, cytosine and guanine. Two strands of double helix are linked through hydrogen bonds, weak chemical bonds between adenine- thymidine and cytosine- guanine. These bonds guarantee to keep constant the distance between two strands and allow replication mechanism starting. Indeed, when DNA must be replicated or transcribed into mRNA, double stranded helix opens and DNA polymerase works to perfectly replicate DNA. DNA polymerase is a crucial enzyme for cellular life: during cellular duplication, it provides to daughter cells the same genetic material of mother cell, without loosing information.
DNA replication is an easy and strictly controlled process. Indeed, a series of enzymes guarantees that none error is introduced into the new sequence in order to preserve cellular genetic profile. If any mistake happens, cellular duplication will be blocked in order to repair the damage; if it’s not possible to overcome the problem, cell should be addressed to apoptosis –programmed cell death- in order to protect the whole organism from genetic alteration.
Unfortunately, in certain circumstances, DNA repair machinery and proofreading activity of DNA polymerase are not enough to correct DNA replication errors and these mistakes are introduced into the genetic code of daughter cells.
In the most of cases, these alterations, namely mutations, have not any consequences in terms of protein functionality. We remember that genetic information encoded in DNA is translated through mRNA into proteins that maintain all cellular activities. In other cases, mutations could alter protein activity, determining loss of function or gain of function. In both cases, some cellular activity is altered and, as a consequence, some disease could arise. All genetically determined diseases show mutations in one or more genes, due to errors during DNA replication. If these errors happen during germ line cells duplication, this mutation will be transmitted to progeny.
One example of genetic disease is cancer. Numerous genes have been implicated in this pathology and in all kind of cancer, one or more mutations have been identified as responsible of altered cellular proliferation, the principal feature of cancer cells. Some mutations arise in genes that encode proteins promoting cellular proliferation: in this case mutations cause a gain of function. Otherwise, mutations cause a loss of function and alter negative control mechanism. In both cases, the result is lack of proliferation control and tumour growth. The role of genetics in cancer research is crucial because this discipline allows determining the mechanism of mutagenesis. Mutated genes and, in consequence, mutated proteins should be possible target for therapies, thus it becomes fundamental still working on genome and proteome in order to figure out useful drugs.