Reference: Bezalel-Buch R, et al. (2026) Opposing regulation by Rev1 of DNA polymerase zeta activity on damaged versus undamaged DNA. Nucleic Acids Res 54(11)

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Abstract


The Rev1 deoxycytidyl transferase functions as a scaffold protein for DNA polymerase ζ (Pol ζ)-mediated translesion synthesis (TLS). Biochemical studies with yeast enzymes indicate that Rev1 plays a dual regulatory role in TLS, stimulating Pol ζ activity at sites of damage but inhibiting its activity on undamaged DNA. An evolutionary conserved N-terminal alpha-helical motif (M1), located 10-20 amino acids upstream of Rev1's single BRCT domain, is required for the inhibitory activity of Rev1 on undamaged DNA. Mutations in the M1 motif result in a stimulation of Pol ζ replication activity on both undamaged and damaged DNA. Yeast cells carrying a REV1 mutant lacking the M1 motif show a four-fold increase in complex mutations without significantly affecting overall spontaneous mutation rates. A catalytically inactive mutant of Rev1 still exerts these regulatory functions. However, regulation requires that Rev1 and Pol ζ form a stable complex, and that this complex is coordinated by the replication clamp PCNA.

Reference Type
Journal Article
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Bezalel-Buch R, Stith C, Makarova AV, Binz SK, Burgers PM
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