2025-12-03 国立遺伝学研究所
図: ゲノムDNAにはMCMヘリカーゼが転写している遺伝子以外の領域に広く結合しており、MCMヘリカーゼのリン酸化はリン酸化酵素DDKと脱リン酸化酵素RIF1-PP1により拮抗的に制御されている。リン酸化されたMCMヘリカーゼにTRESLIN-MTBP複合体が呼び込まれることで、複製開始する場所が決定される。
<関連情報>
- https://www.nig.ac.jp/nig/ja/2025/12/research-highlights_ja/pr20251203.html
- https://www.nig.ac.jp/nig/images/research_highlights/PR20251203.pdf
- https://www.nature.com/articles/s41467-025-66278-7
制御されたTRESLIN-MTBPローディングはヒトDNA複製の開始領域と複製タイミングを制御する Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication
Xiaoxuan Zhu,Atabek Bektash,Yuki Hatoyama,Sachiko Muramatsu,Shin-Ya Isobe,Chikashi Obuse,Atsushi Toyoda,Yasukazu Daigaku,Chun-Long Chen & Masato T. Kanemaki
Nature Communications Published:02 December 2025
DOI:https://doi.org/10.1038/s41467-025-66278-7
Abstract
Replication origins in human cells form clusters ranging from tens to hundreds of kilobases called initiation zones (IZs), typically located in intergenic regions between active genes. On a larger megabase scale, chromosomes replicate following temporally defined replication timing (RT), where euchromatic regions replicate early, and heterochromatic regions replicate late. Although the stochastic model of IZ firing with a temporally regulated limiting factor can explain RT formation, this limiting factor in human cells remains unclear. To investigate the relationship between IZ and RT, we map the temporal firing pattern of IZs and examine the genome-wide distributions of replication licensing and firing factors in human cells. We identify TRESLIN-MTBP as a key limiting firing factor for replication initiation. Its loading onto phosphorylated MCM2–7 double hexamer (MCM-DH) is controlled by the opposing phosphorylation events on MCM-DH by Dbf4-dependent kinase and RIF1-Protein Phosphatase 1, which ultimately determine IZs and establish RT.
