Physical and functional interactions between nucleosomes and Rad27, a critical component of DNA processing during DNA metabolism

Highly conserved eukaryotic histones are polybasic proteins that package DNA into nucleosomes, a building block of chromatin, allowing extremely long DNA molecules to form compact and discrete chromosomes. The histone N‐terminal tails that extend from the nucleosome core act as docking sites for many proteins through diverse post‐translational modifications, regulating various DNA transactions. In this report, we present evidence that the nucleosomes can positively regulate the enzymatic activity of Rad27 (yeast Fen1), a major processing enzyme important for Okazaki fragment in eukaryotes. We found that individual histones, histone octamers, and nucleosomes are able to stimulate Rad27 in a manner dependent on the N‐terminal tails of histones. Kinetic analyses suggest that an increase in catalytic efficiency of Rad27 was mainly due to increased affinity between DNA substrates and Rad27. It appears that the physical interaction in vivo between histones and Rad27 results in the enrichment of Rad27 in the vicinity of chromatin, increasing the availability of Rad27 for various DNA metabolisms. These results indicate that nucleosomes are not a mere structural component of chromatin, but an active regulator of DNA metabolisms that serves to ensure the efficient and faithful processing of structural intermediates arising during DNA transactions. Histones package DNA into nucleosomes, allowing long DNA molecules to form compact chromosomes. The histone N‐terminal tails that extend from the nucleosome core act as docking sites for many proteins. Yeon‐Soo Seo and colleagues now report that Rad27, a nuclease with a key role in DNA metabolism and repair, interacts with the N‐terminal tails of histones. This interaction positively regulates the nuclease activity of Rad27 and increases the local concentration of Rad27 at chromatin. Thus, aside from their structural role, histones may also serve as active regulators of DNA replication and repair through regulating the activity of chromatin‐binding proteins such as Rad27.