NEIL3: A unique DNA glycosylase involved in interstrand DNA crosslink repair

Oswalt, Leah E.; Eichman, Brandt F.

doi:10.1016/j.dnarep.2024.103680

Cited by 2 publications

(1 citation statement)

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“…On the other hand, both EtU and C8-AlkU were robustly excised, raising the possibility of BER involvement in their removal. Additionally, some other human DNA glycosylases recognizing pyrimidine lesions, such as TDG, NEIL3 or NTHL1 [ 41 , 79 , 80 ], could be active against EtU, C8-AlkU or C8-AlkC, but they were not tested here.…”

Section: Discussionmentioning

confidence: 99%

Repair and DNA Polymerase Bypass of Clickable Pyrimidine Nucleotides

Endutkin,

Yudkina,

Zharkov

et al. 2024

Biomolecules

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Clickable nucleosides, most often 5-ethynyl-2′-deoxyuridine (EtU), are widely used in studies of DNA replication in living cells and in DNA functionalization for bionanotechology applications. Although clickable dNTPs are easily incorporated by DNA polymerases into the growing chain, afterwards they might become targets for DNA repair systems or interfere with faithful nucleotide insertion. Little is known about the possibility and mechanisms of these post-synthetic events. Here, we investigated the repair and (mis)coding properties of EtU and two bulkier clickable pyrimidine nucleosides, 5-(octa-1,7-diyn-1-yl)-U (C8-AlkU) and 5-(octa-1,7-diyn-1-yl)-C (C8-AlkC). In vitro, EtU and C8-AlkU, but not C8-AlkC, were excised by SMUG1 and MBD4, two DNA glycosylases from the base excision repair pathway. However, when placed into a plasmid encoding a fluorescent reporter inactivated by repair in human cells, EtU and C8-AlkU persisted for much longer than uracil or its poorly repairable phosphorothioate-flanked derivative. DNA polymerases from four different structural families preferentially bypassed EtU, C8-AlkU and C8-AlkC in an error-free manner, but a certain degree of misincorporation was also observed, especially evident for DNA polymerase β. Overall, clickable pyrimidine nucleotides could undergo repair and be a source of mutations, but the frequency of such events in the cell is unlikely to be considerable.

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Section: Discussionmentioning

confidence: 99%