Markel Martinez-Carranza "The archaeal core replisome: many ways to look at it"

Many of the replication factors that help replicate DNA act in concert in a dynamic protein complex referred to as the replisome. Using an integrative structural biology approach, combining NMR, X-ray crystallography and cryo-EM with DNA polymerization assays, our aim is to decipher the molecular mechanisms required for the assembly of the archaeal replisome, which is a distant and simpler relative of the eukaryotic one. Our latest work focused on the essential replisome component Replication Protein A (RPA), which plays a pivotal role in DNA replication, avidly coating exposed single-stranded DNA as soon as the double-helix is unwound. We unveiled how RPA uses a conserved C-terminal winged-helix domain to interact with two key actors of the replisome regulating their activity: the DNA primase (PriSL) and the replicative DNA polymerase (PolD). We present multiple structures explaining a conserved mechanism for RPA-mediated interactions, which shares its ancestor with eukaryotic RPA and the CST telomere maintenance complex.