Nucleosome assembly and disassembly activity of GRWD1, a novel Cdt1-binding protein that promotes pre-replication complex formation

Masahiro Aizawa, Nozomi Sugimoto, Shinya Watanabe, Kazumasa Yoshida, Masatoshi Fujita

研究成果: Contribution to journalArticle査読

9 被引用数 (Scopus)

抄録

GRWD1 was previously identified as a novel Cdt1-binding protein that possesses histone-binding and nucleosome assembly activities and promotes MCM loading, probably by maintaining chromatin openness at replication origins. However, the molecular mechanisms underlying these activities remain unknown. We prepared reconstituted mononucleosomes from recombinant histones and a DNA fragment containing a nucleosome positioning sequence, and investigated the effects of GRWD1 on them. GRWD1 could disassemble these preformed mononucleosomes in vitro in an ATP-independent manner. Thus, our data suggest that GRWD1 facilitates removal of H2A-H2B dimers from nucleosomes, resulting in formation of hexasomes. The activity was compromised by deletion of the acidic domain, which is required for efficient histone binding. In contrast, nucleosome assembly activity of GRWD1 was not affected by deletion of the acidic domain. In HeLa cells, the acidic domain of GRWD1 was necessary to maintain chromatin openness and promote MCM loading at replication origins. Taken together, our results suggest that GRWD1 promotes chromatin fluidity by influencing nucleosome structures, e.g., by transient eviction of H2A-H2B, and thereby promotes efficient MCM loading at replication origins.

本文言語英語
ページ(範囲)2739-2748
ページ数10
ジャーナルBiochimica et Biophysica Acta - Molecular Cell Research
1863
11
DOI
出版ステータス出版済み - 11 1 2016

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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