Apr 12, 2020

Visualizing Rev1 Catalyze Protein-template DNA Synthesis

BioRxiv : the Preprint Server for Biology
T. M. WeaverBret D Freudenthal

Abstract

During DNA replication, replicative DNA polymerases may encounter DNA lesions, which can stall replication forks. One way to prevent replication fork stalling is through the recruitment of specialized translesion synthesis (TLS) polymerases that have evolved to incorporate nucleotides opposite DNA lesions. Rev1 is a specialized TLS polymerase that bypasses abasic sites as well as minor-groove and exocyclic guanine adducts. It does this by using a unique protein-template mechanism in which the template base is flipped out of the DNA helix and the incoming dCTP hydrogen bonds with an arginine side chain. To observe Rev1 catalysis at the atomic level, we employed time-lapse X-ray crystallography. We found that Rev1 flips out the template base prior to binding the incoming nucleotide. Binding the incoming nucleotide changes the conformation of the DNA substrate to orient it for nucleotidyl transfer, and this is not coupled to large structural changes in the protein like those observed with other DNA polymerases. Moreover, we found that following nucleotide incorporation, Rev1 converts the pyrophosphate product to two mono-phosphates, which drives the reaction in the forward direction. Following nucleotide incorporation, the hydroge...Continue Reading

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Mentioned in this Paper

CD34
Gene Editing
RNPC3
Red blood cells, blood product
DNA Aptamers
PSMA7 gene
Nucleic Acid Sequencing
Sickle Hemoglobin
Etiology
Cell Differentiation Process

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