Mutations on WFYY motif alters the PrimPol activity: Structural insights from atomistic MD simulations

PrimPol is a Primase and Polymerase enzyme with significance in reinitiating DNA replication

at stalled replication forks. The WFYY motif of PrimPol was previously reported to play an

essential role in stabilizing the incoming 3′-nucleotide. The W87G and Y90D mutations

significantly reduced the primase and polymerase activity of PrimPol. We have performed

microsecond scale molecular dynamics on wildtype, W87G, F88L, Y89D, and Y90D complexes

to investigate the structural implications of the single point mutations in PrimPol polymerase

activity. This study points towards the possible changes in the interdomain communication in

the PrimPol enzyme associated with single point mutations in the conserved motifs of the

enzyme.