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Deubiquitinating PCNA: a downside to DNA damage tolerance

Monoubiquitination of the processivity clamp, PCNA, facilitates the replicative bypass of DNA lesions by recruiting damage-tolerant polymerases. In undamaged cells, deubiquitination of PCNA by the deubiquitinating enzyme USP1 reveals a possible safeguard mechanism against the mutagenic effect of these polymerases. Intriguingly, USP1 itself seems to be downregulated by a damage-induced autocatalytic cleavage event.

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Figure 1: Strategies for inducing DNA damage tolerance.

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Ulrich, H. Deubiquitinating PCNA: a downside to DNA damage tolerance. Nat Cell Biol 8, 303–305 (2006). https://doi.org/10.1038/ncb0406-303

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