Rate-limiting enzymes in nucleotide metabolism synchronize nucleotide biosynthesis and chromatin formation.

ABSTRACT: Chromatin formation requires both an adequate nucleotide supply and histone availability. Newly synthesized histones are escorted by histone chaperones that mediate their orderly transfer from ribosomes to DNA. While nucleotide and histone synthesis are the two major biosynthetic processes required for chromatin assembly, how these processes are coordinated remains unknown. Phosphoribosyl pyrophosphate synthetases (PRPSs), which catalyze the first and rate-limiting step in nucleotide biosynthesis, form a complex with PRPS-associated proteins (PRPSAPs). Using a rapid degron system in multiple human cell lines, we show that PRPS enzymes, together with PRPSAPs, play a key role in early histone maturation independent of their nucleotide biosynthetic function. Depletion of either PRPS1 or PRPSA

SUBMITTER: Srivastava S 

PROVIDER: S-EPMC12695082 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature