Official websites use. Share sensitive information only on official, secure websites. Competing Interests: The authors have declared that no competing interests exist. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In vertebrates, APEX1 knockouts are embryonic lethal, and only a handful of knockout cell lines are known.
Two stable knockout lines were obtained, one carrying two single-base deletion alleles and one single-base insertion allele in exon 3, another homozygous in the single-base insertion allele.
However, the knockout lines retained a nearly wild-type sensitivity to oxidizing agents hydrogen peroxide and potassium bromate. Interestingly, despite the increased MMS cytotoxicity, we observed no additional increase in AP sites in knockout cells upon MMS treatment, which could indicate their conversion into more toxic products in the absence of repair. Overall, the relatively mild cell phenotype in the absence of APEX1-dependent BER suggests that mammalian cells possess mechanisms of tolerance or alternative repair of AP sites.
Many endogenous and environmental factors generate a steady stream of lesions in cellular DNA. Base excision repair BER is the system primarily responsible for the removal of small non-bulky lesions from DNA [ 2 , 3 ]. BER is initiated by various DNA glycosylases, each of which is specific to a characteristic type of damage. AP sites are non-instructional and thus strongly mutagenic, often directing dAMP misincorporation [ 7 , 8 ].
In addition, AP sites are toxic for cells via multiple mechanisms, including DNA strand breakage, transcription errors, and covalent trapping of DNA-bound proteins such as histones and topoisomerases [ 9 β 12 ].
