**1. Introduction**

Even in the earliest stages of evolution, damage to the genome was presumably a fundamental problem for life. Thus it is likely that organisms developed processes for repairing genome damages very early. Such repair processes are ordinarily restorative, designed to reestablish the original undamaged genome sequence. During the course of the evolution of lineages leading to mammals, DNA repair processes became more complex, and acquired additional capabilities. One such example is the employment of the DNA double-strand break repair process of nonhomologous end joining in the generation of immunological diversity [1].

In chromatin, epigenetic alterations are an integral part of DNA repair processes [2]. Although most epigenetic alterations introduced during DNA repair are transient with restoration of the epigenetic pattern that existed prior to repair, some are long lasting. Epigenetic alterations can enhance or inhibit gene expression without changing the DNA base pair sequence. Examples of epigenetic alterations are hyper- or hypomethylation of cytosines in the DNA sequence, increased or decreased histone H3 and H4 acetylation by histone acetyltransferases or histone deacetylases, and increased or decreased histone methylation by histone methyltransferases or histone demethylases.

In humans, the oxygen demands of the brain are high, constituting about 20% of total body oxygen consumption, while the mass of the brain is only about 2% of body mass [3]. This results in elevated release of reactive oxygen species in the brain that, in turn, cause oxidative DNA damages. Because damages are prevalent, processes that repair DNA damages have a vital role in maintaining the health of brain neurons, and these DNA repair processes can cause epigenetic alterations.

When DNA repair processes are impaired or insufficient, the result can be improper (non-adaptive) epigenetic alterations. Such improper epigenetic alterations in neurons are likely an important underlying cause of certain addictions and neurodegenerative diseases. Several addictive agents cause increased DNA damage in neurons resulting in increased dependence on DNA repair. Addictions are associated with characteristic persistent patterns of epigenetic alterations in the brain. In several neurodegenerative diseases the neurological impairments are caused by inherited mutations in genes that encode proteins employed in DNA repair. These diseases are associated with particular patterns of epigenetic alterations in neurons. It is likely that the neurological impairments suffered by individuals during addiction or neurodegenerative disease are caused, at least in part, by epigenetic alterations resulting from insufficient or faulty DNA repair. That is, insufficient or faulty DNA repair may produce epigenetic alterations that have long-lasting negative consequences at the level of gene expression that manifest as neurological impairment.

Zovkic et al. [4] noted that learning and memory can be broadly defined as lasting alterations of a behavioral output produced in response to a transient environmental input. In order for a brief stimulus to cause a persistent change in behavior, neurons need to undergo some kind of molecular alterations that stabilize a memory into an enduring set of cellular marks. As reviewed by Bird in 2002 [5], in mammals, DNA methylation is adapted for specific cellular memory in development, even over successive cell divisions. This observation of cellular memory indicated that epigenetic mechanisms could provide a molecular basis for neuronal memory formation and maintenance in non-replicating neurons [4]. In addition to DNA methylation/demethylation, it is now known that other mechanisms such as chromatin histone acetylation and histone methylation can also cause persistent epigenetic changes [6].

 In the sections below, we review evidence for the following ideas. Neuronal activity causes DNA damages, and repair processes are required to deal with these damages. Such repair processes involve epigenetic alterations, some of which are long lasting. Individuals, addicted to abuse of certain substances that cause DNA damage, have long-lasting epigenetic alterations in brain neurons that appear to be related to the dependency. Also, inherited inability to adequately repair DNA damages can cause epigenetic alterations in neurons associated with neurodegenerative disease. However, long-lasting epigenetic alterations can also be adaptively beneficial. Cognitive functions such as memory and learning in response to external stimuli appear to depend, at least in part, on persistent epigenetic alterations arising during DNA repair processes.

*The Role of DNA Repair and the Epigenetic Markers Left after Repair in Neurologic Functions… DOI: http://dx.doi.org/10.5772/intechopen.83477* 
