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

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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… Click to show full abstract

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 The replication protein A complex plays a role in the assembly of new nucleosomes on newly replicated DNA strands. 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.

Keywords: dna replication; stranded dna; replication coupled; nucleosome assembly; replication

Journal Title: Science
Year Published: 2017

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