Human PrimPol mutation associated with high myopia has a DNA replication defect.
Bottom Line: Here, we examined whether this mutation resulted in any changes in the molecular and cellular activities associated with human PrimPol.We also demonstrate that the decreased activity of PrimPolY89D is associated with reduced affinities for DNA and nucleotides, resulting in diminished catalytic efficiency.This mutation also reduces cell viability after DNA damage and significantly slows replication fork rates in vivo.
Affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.Show MeSH
Related in: MedlinePlus
Mentions: To gain further insights into how the Y89D mutant form of PrimPol may contribute to the myopic phenotype observed in human patients, we studied the influence of PrimPolY89D on DNA replication in damaged and undamaged cells. We utilized a DT40 PrimPol deleted cell line (PrimPol −/−) (4) to examine the ability of PrimPolY89D to complement this loss, as previously reported for other mutant forms of PrimPol (14). We stably expressed human PrimPolY89D at similar levels to WT PrimPol in PrimPol knockout cells (Figure 8A), with no obvious effects on cell growth.
Affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.