Structure of the human Rev1-DNA-dNTP ternary complex

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Y-family DNA polymerases exhibit diverse replication strategies for DNA lesions.
• Yeast Rev1 employs a unique mechanism where the polymerase controls nucleotide and template base selection.

Purpose of the Study:

• To investigate the conservation of yeast Rev1's radical replication strategy in human Rev1.
• To elucidate the structural features of human Rev1 that facilitate translesion DNA synthesis.

Main Methods:

• Comparative structural analysis of yeast and human Rev1 ternary complexes.
• Identification and characterization of unique structural inserts (I1 and I2) in human Rev1.

Main Results:

• Key elements of yeast Rev1's replication strategy, including template G eviction and surrogate pairing, are conserved in human Rev1.
• Human Rev1 features two large inserts (I1 and I2) augmenting its catalytic core.
• Insert I1 may mediate protein-protein interactions, while I2 acts as a flap over the template G binding pocket.

Conclusions:

• Human Rev1 conserves a unique DNA replication strategy with yeast Rev1.
• Novel structural features in human Rev1 enhance its capacity for efficient and accurate translesion DNA synthesis.
• These features are crucial for processing bulky DNA adducts, such as N(2)-deoxyguanosine adducts, in human cells.