2026-09-07 国立遺伝学研究所
図1：ヒト細胞のゲノムDNA複製における複製開始反応の模式図。
＜関連情報＞
- https://www.nig.ac.jp/highlights/14997/
- https://genesdev.cshlp.org/content/early/2026/09/03/gad.353714.126
MCM10とRECQL4は、複製開始時のCMGヘリカーゼ活性化において、協調的かつ重複した役割を担っている MCM10 and RECQL4 have cooperative and redundant roles in activating the CMG helicase during the replication initiation
Atabek Bektash,Xiaoxuan Zhu,Yuki Hatoyama,Atsushi Toyoda and Masato T. Kanemaki
Genes Development Published: September 4, 2026
DOI:10.1101/gad.353714.126
Abstract
DNA replication initiation requires activation of the CMG helicase to establish the replisome. This process involves the extrusion of single-stranded DNA (ssDNA) from the central channel of MCM double hexamers, allowing the two CMG helicases to pass each other; however, the factors that mediate this process in human cells remain unclear. We show that degron-mediated depletion of either MCM10 or RECQL4 alone causes mild replication defects, whereas simultaneous depletion of both proteins severely impairs CMG activation. ChIP-seq analyses demonstrate that RECQL4 localizes to replication initiation zones (IZs) independently of MCM10, whereas MCM10 recruitment to IZs is enhanced upon RECQL4 depletion, consistent with partially redundant roles during CMG activation. Rescue experiments further indicate that RECQL4 cooperates with MCM10 through direct interaction, and that their ssDNA-binding activity underlies their functional overlap. We propose that MCM10 and RECQL4 act cooperatively and redundantly to promote CMG activation.
