Processing of thymine glycol in a clustered DNA damage site; Mutagenic or cytotoxic

Bellon, S.*; Shikazono, Naoya; Cunniffe, S. M. T.*; Lomax, M.*; O'Neill, P.*

The potential for genetic change arising from the effects of clustered damage sites is high. We have investigated whether clusters containing thymine glycol (Tg) are highly mutagenic or lead to potentially cytotoxic lesions, when closely opposed to either 8-oxo-7,8-dihydroguanine (8-oxoG) or an AP site. We have shown that double strand breaks (DSBs) arise when Tg is opposite to an AP site, either through attempted repair or at replication. In contrast, 8-oxoG opposite to Tg in a cluster protects against DSB formation but does enhance the mutation frequency at the site of 8-oxoG relative to that at a single 8-oxoG.