Editing Mutagenesis (section)

===Modification of bases===
Bases may be modified endogenously by normal cellular molecules. For example, [[DNA methylation|DNA may be methylated]] by [[S-adenosylmethionine]], thus altering the expression of the marked gene without incurring a mutation to the DNA sequence itself. [[Histone|Histone modification]] is a related process in which the histone proteins around which DNA coils can be similarly modified via methylation, phosphorylation, or acetylation; these modifications may act to alter gene expression of the local DNA, and may also act to denote locations of damaged DNA in need of repair. DNA may also be [[Glycosylation|glycosylated]] by [[reducing sugar]]s.

Many compounds, such as PAHs, [[aromatic amines]], [[aflatoxin]] and [[pyrrolizidine alkaloid]]s, may form [[reactive oxygen species]] catalyzed by cytochrome P450. These metabolites form adducts with the DNA, which can cause errors in replication, and the bulky aromatic adducts may form stable intercalation between bases and block replication. The adducts may also induce conformational changes in the DNA. Some adducts may also result in the [[depurination]] of the DNA;<ref>{{Cite journal 
| last1 = Melendez-Colon | first1 = V. J. 
| last2 = Smith | first2 = C. A. 
| last3 = Seidel | first3 = A. 
| last4 = Luch | first4 = A. 
| last5 = Platt | first5 = K. L. 
| last6 = Baird | first6 = W. M. 
| title = Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzoa, lpyrene or its diol epoxides 
| journal = Proceedings of the National Academy of Sciences of the United States of America 
| volume = 94 
| issue = 25 
| pages = 13542–13547 
| year = 1997 
| pmid = 9391062 
| pmc = 28342 | doi=10.1073/pnas.94.25.13542
| bibcode = 1997PNAS...9413542M| doi-access = free 
}}</ref> it is, however, uncertain how significant such depurination as caused by the adducts is in generating mutation.

[[Alkylation]] and [[arylation]] of bases can cause errors in replication. Some alkylating agents such as N-[[Nitrosamine]]s may require the catalytic reaction of cytochrome-P450 for the formation of a reactive alkyl cation. N<sup>7</sup> and O<sup>6</sup> of guanine and the N<sup>3</sup> and N<sup>7</sup> of adenine are most susceptible to attack. N<sup>7</sup>-guanine adducts form the bulk of [[DNA adducts]], but they appear to be non-mutagenic. Alkylation at O<sup>6</sup> of guanine, however, is harmful because [[excision repair]] of O<sup>6</sup>-adduct of guanine may be poor in some tissues such as the brain.<ref>{{Cite journal 
| last1 = Boysen | first1 = G. 
| last2 = Pachkowski | first2 = B. F. 
| last3 = Nakamura | first3 = J. 
| last4 = Swenberg | first4 = J. A. 
| title = The Formation and Biological Significance of N7-Guanine Adducts 
| doi = 10.1016/j.mrgentox.2009.05.006 
| journal = Mutation Research/Genetic Toxicology and Environmental Mutagenesis 
| volume = 678 
| issue = 2 
| pages = 76–94 
| year = 2009 
| pmid = 19465146 
| pmc =2739241 
}}</ref> The O<sup>6</sup> methylation of guanine can result in G to A [[Transition (genetics)|transition]], while O<sup>4</sup>-methylthymine can be mispaired with guanine. The type of the mutation generated, however, may be dependent on the size and type of the adduct as well as the DNA sequence.<ref>{{Cite journal 
| last1 = Loechler | first1 = E. L. 
| title = The role of adduct site-specific mutagenesis in understanding how carcinogen-DNA adducts cause mutations: Perspective, prospects and problems 
| journal = Carcinogenesis 
| volume = 17 
| issue = 5 
| pages = 895–902 
| year = 1996 
| pmid = 8640935
 | doi=10.1093/carcin/17.5.895
| doi-access =  
}}</ref>

Ionizing radiation and reactive oxygen species often oxidize guanine to produce [[8-oxoguanine]].

{{See also|Epigenetics}}

[[Image:brokechromo.jpg|thumb|right|180px|Arrows indicates chromosomal breakages due to DNA damage.]]