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. 2021 Jan 5;11(4):1177–1197. doi: 10.1016/j.jcmgh.2020.12.013

Figure 2.

Figure 2

Mutations caused by 8-oxoG. (A) ROS-mediated oxidation of guanine (G) generates C:8-oxoG base pairs that are normally repaired by OGG1-initiated base excision repair. (B) 8-oxoG has base-pairing properties similar to thymine (T); therefore 8-oxoG in DNA during S-phase of the cell cycle leads to preferential insertion of adenine (A) opposite the 8-oxoG instead of cytosine (C) by replicative DNA polymerases. (C) A:8-oxoG mispairs can be recognized and repaired by MMR. However, if this mismatch is left unrepaired, a second round of replication will lead to C:G→A:T transversion mutation in one daughter cell. (D) Deoxyguanosine triphosphate (dGTP) in the nucleotide pool can be oxidized and incorporated into the nascent DNA strand opposite an A during replication, which can be repaired by MMR. However, A:8-oxo-G mispairs also can be processed through inappropriate MUTYH-initiated base excision repair, leading to the formation of C:8-oxo-G pairs, which could be further repaired by OGG1, generating an A:T→C:G transversion mutation. To avoid this, it is believed that cells avoid MUTYH activity during replication, giving preference to the MMR system. Therefore, lack of MMR activity is particularly an issue for highly proliferative tissues under oxidative environment such as gastrointestinal tract.