title: RPA binds histone H3-H4 and functions in DNA replication-coupled nucleosome assembly.
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.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.|Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors.forename: He
authors.initials: H
authors.lastname: Leng
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for Cardiovascular Regeneration, DeBakey Heart and Vascular Center, Houston Methodist, Houston, TX 77030, USA.
authors.forename: Kaifu
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. li.qing@pku.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D056488:Histone Chaperones; D006657:Histones; D009707:Nucleosomes; C082728:RFA1 protein, S cerevisiae; C082727:RFA2 protein, S cerevisiae; C093847:RPA14 protein, S cerevisiae; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; D012318:RNA Polymerase I