2023-04-05 ミュンヘン大学(LMU)
細胞分裂のためのDNA複製には、通常、このクロマチン構造を解きほぐす必要があるとされていたが、ドイツのLMUのバイオ医学センター(BMC)の分子生物学者であるクリストフ・F・クラート氏率いるチームが、それが完全な真実ではないことを明らかにした。
研究者らは、ジャーナル「Nature」に報告し、ゲノムの特定の場所である複製開始点では、特徴的な核小体構造が、複製を開始させるために極めて重要であることを示した。
この研究により、細胞分裂やがん治療の新しいアプローチにつながる知見が得られる可能性がある。
<関連情報>
- https://www.lmu.de/en/newsroom/news-overview/news/dna-packaging-the-useful-obstacle.html
- https://www.nature.com/articles/s41586-023-05926-8
複製起点におけるクロマチン組織の確立と機能 Establishment and function of chromatin organization at replication origins
Erika Chacin,Karl-Uwe Reusswig,Jessica Furtmeier,Priyanka Bansal,Leonhard A. Karl,Boris Pfander,Tobias Straub,Philipp Korber & Christoph F. Kurat
Nature Published:05 April 2023
DOI:https://doi.org/10.1038/s41586-023-05926-8
Abstract
The origin recognition complex (ORC) is essential for initiation of eukaryotic chromosome replication as it loads the replicative helicase—the minichromosome maintenance (MCM) complex—at replication origins1. Replication origins display a stereotypic nucleosome organization with nucleosome depletion at ORC-binding sites and flanking arrays of regularly spaced nucleosomes2,3,4. However, how this nucleosome organization is established and whether this organization is required for replication remain unknown. Here, using genome-scale biochemical reconstitution with approximately 300 replication origins, we screened 17 purified chromatin factors from budding yeast and found that the ORC established nucleosome depletion over replication origins and flanking nucleosome arrays by orchestrating the chromatin remodellers INO80, ISW1a, ISW2 and Chd1. The functional importance of the nucleosome-organizing activity of the ORC was demonstrated by orc1 mutations that maintained classical MCM-loader activity but abrogated the array-generation activity of ORC. These mutations impaired replication through chromatin in vitro and were lethal in vivo. Our results establish that ORC, in addition to its canonical role as the MCM loader, has a second crucial function as a master regulator of nucleosome organization at the replication origin, a crucial prerequisite for efficient chromosome replication.
