Rev7, the regulatory subunit of Polζ, undergoes UV-induced and Cul4-dependent degradation

In eukaryotic cells, Rev7 interacts with Rev3 and functions as a regulatory subunit of Polζ, a translesion DNA synthesis (TLS) polymerase. In addition to its role in TLS, mammalian Rev7, also known as Mad2B/Mad2L2, participates in multiple cellular activities including cell cycle progression and double-strand break repair through its interaction with several proteins. Here we show that in mammalian cells, Rev7 undergoes ubiquitin/proteasome-mediated degradation upon UV irradiation in a time-dependent manner. We identified the Rev7 N-terminal destruction box as the degron and Cul4A/B as putative E3 ligases in this process. We also show that the nucleotide excision repair (NER) pathway protein HR23B physically interacts and colocalizes with Rev7 in the nuclear foci after UV irradiation and protects Rev7 from accelerated degradation. Furthermore, a similar Rev7 degradation profile was observed in cells treated with the UV-mimetic agent 4-nitroquinoline 1-oxide but not with cisplatin or camptothecin, suggesting a role of the NER pathway protein(s) in UV-induced Rev7 degradation. These data and the observation that cells deficient in Rev7 are sensitized to UV irradiation while excessive Rev7 protects cells from UV-induced DNA damage provide a new insight into the potential interplay between TLS and NER.