Genetic and physical interactions between Pol? and Rev1 in response to UV-induced DNA damage in mammalian cells.

In response to UV irradiation, translesion DNA synthesis (TLS) utilizes specialized DNA polymerases to bypass replication-blocking lesions. In a well-established polymerase switch model, Pol? is thought to be a preferred TLS polymerase to insert correct nucleotides across from the thymine dimer, and Rev1 plays a scaffold role through physical interaction ...
with Pol? and the Rev7 subunit of Pol? for continual DNA synthesis. Defective Pol? causes a variant form of xeroderma pigmentosum (XPV), a disease with predisposition to sunlight-induced skin cancer. Previous studies revealed that expression of Rev1 alone is sufficient to confer enhanced UV damage tolerance in mammalian cells, which depends on its physical interaction with Pol? but is independent of Pol?, a conclusion that appears to contradict current literature on the critical roles of Pol? in TLS. To test a hypothesis that the Rev1 catalytic activity is required to backup Pol? in TLS, we found that the Rev1 polymerase-dead mutation is synergistic with either Pol? mutation or the Pol?-interaction mutation in response to UV-induced DNA damage. On the other hand, functional complementation of polH cells by Pol? relies on its physical interaction with Rev1. Hence, our studies reveal critical interactions between Rev1 and Pol? in response to UV damage.
Mesh Terms:
DNA Damage, DNA-Directed DNA Polymerase, Genomic Instability, HEK293 Cells, Humans, Mutation, Nucleotidyltransferases, Protein Interaction Maps, Ultraviolet Rays
Sci Rep
Date: Dec. 01, 2020
Download Curated Data For This Publication
235599
Switch View:
  • Interactions 1