biostudies-literatureUnknown42(1)Furrer AAlkylating agents often generate 3-methylcytosine (3meC) lesions that are efficiently repaired by AlkB homologues. If AlkB homologue proteins are not functional, or the number of 3meC lesions exceeds the cellular repair capacity, the damage will persist in the genome and become substrate of DNA polymerases (Pols). Though alkylating agents are present in our environment and used in the clinics, currently nothing is known about the impact of 3meC on the accuracy and efficiency of human Pols. Here we compared the 3meC bypass properties of six human Pols belonging to the three families: B (Pol δ), X (Pols β and λ) and Y (Pols κ, ι and η). We show that under replicative conditions 3meC impairs B-family, blocks X-family, but not Y-family Pols, in particular Pols η and ι. These Pols successfully Nucleic acids research553-66https://www.ebi.ac.uk/biostudies/studies/S-EPMC3874200biostudies-literatureHandling the 3-methylcytosine lesion by six human DNA polymerases members of the B-, X- and Y-families.PMC3874200van Loon BFurrer AfalseHandling the 3-methylcytosine lesion by six human DNA polymerases members of the B-, X- and Y-families.Alkylating agents often generate 3-methylcytosine (3meC) lesions that are efficiently repaired by AlkB homologues. If AlkB homologue proteins are not functional, or the number of 3meC lesions exceeds the cellular repair capacity, the damage will persist in the genome and become substrate of DNA polymerases (Pols). Though alkylating agents are present in our environment and used in the clinics, currently nothing is known about the impact of 3meC on the accuracy and efficiency of human Pols. Here we compared the 3meC bypass properties of six human Pols belonging to the three families: B (Pol δ), X (Pols β and λ) and Y (Pols κ, ι and η). We show that under replicative conditions 3meC impairs B-family, blocks X-family, but not Y-family Pols, in particular Pols η and ι. These Pols successfully 2014-01-01T00:00:00Z2014 Jan2026-04-30T03:24:12.444Z2019-03-27T01:19:06ZS-EPMC38742002409744310.1093/nar/gkt889