Report

RPA binds histone H3-H4 and functions in DNA replication–coupled nucleosome assembly

+ See all authors and affiliations

Science  27 Jan 2017:
Vol. 355, Issue 6323, pp. 415-420
DOI: 10.1126/science.aah4712

You are currently viewing the abstract.

View Full Text

The platform for building new chromatin

Nucleosomes removed from DNA to facilitate its replication must be replaced quickly to protect the genome. The epigenetic information stored on the parental nucleosomes must also be preserved on the daughter DNA strands. The replication protein A complex (RPA) is a critical component of the DNA replication machinery. RPA binds single-stranded DNA. Liu et al. show that RPA bound to a single-stranded DNA replication fork mimic recruits and promotes the assembly of H3-H4 histone tetramers onto adjacent double-stranded DNA. It also recruits specific H3-H4 chaperones, which facilitate the assembly of new nucleosomes.

Science, this issue p. 415

Abstract

DNA replication–coupled nucleosome assembly is essential to maintain genome integrity and retain epigenetic information. Multiple involved histone chaperones have been identified, but how nucleosome assembly is coupled to DNA replication remains elusive. Here we show that replication protein A (RPA), an essential replisome component that binds single-stranded DNA, has a role in replication-coupled nucleosome assembly. RPA directly binds free H3-H4. Assays using a synthetic sequence that mimics freshly unwound single-stranded DNA at replication fork showed that RPA promotes DNA-(H3-H4) complex formation immediately adjacent to double-stranded DNA. Further, an RPA mutant defective in H3-H4 binding exhibited attenuated nucleosome assembly on nascent chromatin. Thus, we propose that RPA functions as a platform for targeting histone deposition to replication fork, through which RPA couples nucleosome assembly with ongoing DNA replication.

View Full Text