PF3D7_0904800

PF3D7_0904800 (the small-fragment replication protein A1 homologue of Plasmodium falciparum) functions as a negative modulator of homologous recombination in vitro: added in a dose-dependent manner, it suppresses the PfRPA1L-stimulated, PfRad51-mediated homologous pairing and DNA strand exchange reaction (PMID:23631919). Its transcript and protein levels rise following methyl methane sulfonate-induced DNA damage, consistent with participation in the parasite DNA damage response (PMID:23631919). Beyond these two observations from a single study, no further mechanistic detail — including its physical interaction interface with PfRPA1L, in vivo epistasis, or structural basis of regulation — has been characterized in the available corpus.

1. 2013 Medium

   To determine whether the small-fragment RPA1 homologue plays a role in recombination, its effect on the core strand-exchange machinery was tested, establishing it as a dose-dependent negative regulator of PfRPA1L-stimulated, PfRad51-mediated homologous pairing.

   Evidence In vitro DNA strand exchange and homologous pairing assays with recombinant proteins, titrating PfRPA1S against PfRPA1L activity

   PMID:23631919

   Open questions at the time

   • The physical basis of inhibition (direct binding to PfRPA1L, competition for DNA, or another mechanism) is not defined
   • No in vivo genetic epistasis confirms this regulatory role in living parasites
   • Whether the effect is specific to Rad51-mediated exchange or generalizes to other recombination reactions is untested
2. 2013 Low

   To connect the biochemical activity to a physiological trigger, expression was measured after genotoxic stress, showing that PF3D7_0904800 transcript and protein are induced by DNA damage and implicating it in the parasite DNA damage response.

   Evidence Comet assay to confirm DNA damage plus RT-PCR and western blot of PfRPA1S levels after methyl methane sulfonate treatment of P. falciparum

   PMID:23631919

   Open questions at the time

   • Expression-level upregulation was measured in a single study without functional epistasis placing PF3D7_0904800 in a specific repair pathway
   • The signalling route linking DNA damage to induction is unknown
   • Whether induced protein exerts the same inhibitory effect in vivo as observed in vitro is not shown

• How PF3D7_0904800 integrates with the full RPA complex and homologous recombination machinery in living parasites, and the structural/mechanistic basis of its regulatory action, remain unresolved.
• No in vivo knockout, knockdown, or complementation data for PF3D7_0904800
• No structural model or defined interaction interface with PfRPA1L or DNA
• No demonstration of a repair or replication phenotype attributable to PF3D7_0904800