biostudies-literatureUnknownDe Rosa MNIA NIH HHSNIEHS NIH HHSNINDS NIH HHSNCI NIH HHSTelomeres are prone to formation of the common oxidative lesion 8-oxoguanine (8oxoG), and the acute production of 8oxoG damage at telomeres is sufficient to drive rapid cellular senescence. OGG1 and MUTYH glycosylases initiate base excision repair (BER) at 8oxoG sites to remove the lesion or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced senescence, and loss of both glycosylases results in a near complete rescue. Loss of these glycosylases also suppresses 8oxoG-induced telomere fragility and dysfunction, indicating that single-stranded break (SSB) intermediates arising downstream of glycosylase activity impair telomere replication. The failure to initiate BER in glycosylase-deficient cells suppresses PARylation at SSB interbioRxiv : the preprint server for biology2023.04.10.536247https://www.ebi.ac.uk/biostudies/studies/S-EPMC10120708biostudies-literatureOGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced cellular senescence.PMC10120708K99 ES033771R35 ES030396P30 CA047904R01 NS117000R01 CA207342F32 AG067710Nyalapatla PROpresko PLBarnes RPWipf PDe Rosa MfalseOGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced cellular senescence.Telomeres are prone to formation of the common oxidative lesion 8-oxoguanine (8oxoG), and the acute production of 8oxoG damage at telomeres is sufficient to drive rapid cellular senescence. OGG1 and MUTYH glycosylases initiate base excision repair (BER) at 8oxoG sites to remove the lesion or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced senescence, and loss of both glycosylases results in a near complete rescue. Loss of these glycosylases also suppresses 8oxoG-induced telomere fragility and dysfunction, indicating that single-stranded break (SSB) intermediates arising downstream of glycosylase activity impair telomere replication. The failure to initiate BER in glycosylase-deficient cells suppresses PARylation at SSB inter2023-01-01T00:00:00Z2023 Apr2025-08-31T03:07:16.349Z2025-08-31T03:05:09.608ZS-EPMC101207083709058910.1101/2023.04.10.536247