Fig. 7: CHAF1A promotes RAD18/RAD6A-mediated PCNA K164 monoubiquitination in vitro. | Cell Death & Disease

Fig. 7: CHAF1A promotes RAD18/RAD6A-mediated PCNA K164 monoubiquitination in vitro.

From: Chromatin assembly factor 1 subunit A promotes TLS pathway by recruiting E3 ubiquitin ligase RAD18 in cancer cells

Fig. 7

A Schematic of in vitro ubiquitination assay. B In vitro ubiquitination assay of PCNA. The blue asterisk indicates the ubiquitinated RAD18. C The working model of CHAF1A in regulating TLS pathway. Replicative DNA polymerases Pol δ/ε dissociate from the replication fork when the ongoing replication fork encounters replication stress. Then, the ATR-dependent RPA-CHK1 signaling pathway is activated. CHAF1A recruits RAD18 to the stalled replication fork in a DNA binding-dependent manner. RAD18 accelerates PCNA K164 mono-ubiquitination on the stalled replication fork. PCNA K164 mono-ubiquitination promotes the conversion of replicative DNA polymerase Polδ/ε into TLS DNA polymerases (REV1, Pol η, Pol κ and Pol ι). The TLS pathway activated by CHAF1A enhances replication fork restart and damage-tolerant DNA replication, which in turn leads to cancer cell survival under DNA damage.

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