Figure 1.

Circadian rhythm of XPA and NER activity in an unperturbed (A) and UV-damaged (B) cell. (A) The promoter of the XPA gene possesses E-box sequences for CLOCK-BMAL1-driven transcription of the gene, thereby generating a circadian rhythm of XPA and NER activity. The half-life of XPA is short due to the action of an E3 ubiquitin ligase HERC2, which adds ubiquitin to XPA and degrades it through the proteasome pathway, making the amplitude of circadian NER activity robust. (B) Upon UV damage, the ATR checkpoint pathway is activated and then phosphorylates XPA at Ser196. This results in an increase in XPA protein stability by attenuating HERC2-induced XPA ubiquitination and consequently upregulates the NER activity.