DNA polymerase activity is essential for replication, repair, recombination and mutagenesis. DNA polymerases can often bypass DNA lesions that block DNA replication, thereby allowing the replication of damaged DNA. One such DNA polymerase is the distributive enzyme DNA Pol i, which is encoded by the POLI gene. POLI is located on human chromosome 18q21.2, a region often implicated in the etiology of many human cancers. At thymine templates, DNA Pol i is highly error-prone when replicating undamaged DNA in that it favors the misincorporation of guanine over the correct nucleotide, adenosine. DNA Pol i also promotes the replication of damaged DNA by misincorporating deoxynucleotides opposite DNA lesions. DNA Pol i acts sequentially with DNA Pol Ω, which is essential for damage-induced mutagenesis, to complete the DNA lesion bypass. Therefore, replication involving DNA Pol i is likely to be highly mutagenic.