Skip to content
DraconiticResearch
Search Sources API
186,546 studies31 sourcesUpdated 56 min ago
PreprintCC BY-NC 4.0Genes & Development

MCM10 and RECQL4 have cooperative and redundant roles in activating the CMG helicase during the replication initiation

  • Atabek Bektash1,2
  • Xiaoxuan Zhu1
  • Yuki Hatoyama1
  • Atsushi Toyoda3
  • Masato T. Kanemaki1,2,4
4 affiliations
  1. 1Department of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan
  2. 2Graduate Institute for Advanced Studies, SOKENDAI, Mishima, Shizuoka 411-8540, Japan
  3. 3Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan
  4. 4Department of Biological Science, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
Read full textPDFDOICite

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.

Related

  1. DHX30 is a replication stress-responsive R-loop helicase that safeguards genome stability
    E. R. Nedelcu, N. C. Yeo, H. Huber +11
    bioRxivPreprintCC BY-NCFull textMolecular biology & gene regulationbioRxiv
  2. Origins Anywhere and Everywhere: Genome replication requires cooperative activation of thousands of origins in each cell
    Linh Thuy Nguyen, Caitlyn Jean-Baptiste, Julie Gabetto +3
    HALPreprintLicence not statedFull textMolecular biology & gene regulationHAL
  3. A role for CIZ1, a Nuclear Matrix Protein Overexpressed in Cancer Cells, in Controlling the Initiation of DNA Replication
    M. Hossain, M. Tramantano, S. Naik +1
    bioRxivPreprintCC BY-NCFull textMolecular biology & gene regulationbioRxiv
  4. Blood and saliva provide complementary but non-redundant host transcriptomic responses to cancer
    Srinivas V Koduru, Mark Kidd, Abdel Halim
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationCrossref
  5. Human adenine nucleotide translocator isoforms mediate functionally redundant mitochondrial ADP/ATP exchange
    Macie S. Sheridan, John Z. Chan, Steven M. Claypool +1
    Journal of Biological ChemistryPeer-reviewedLicence not statedMolecular biology & gene regulationCrossref

Cite

BibTeXRIS
BibTeX
@misc{bektash2026mcm10,
  title = {{MCM10 and RECQL4 have cooperative and redundant roles in activating the CMG helicase during the replication initiation}},
  author = {Atabek Bektash and Xiaoxuan Zhu and Yuki Hatoyama and Atsushi Toyoda and Masato T. Kanemaki},
  howpublished = {Genes \& Development},
  year = {2026},
  month = nov,
  doi = {10.1101/gad.353714.126},
  url = {https://doi.org/10.1101/gad.353714.126},
  note = {CC BY-NC 4.0},
}
RIS
TY  - UNPB
TI  - MCM10 and RECQL4 have cooperative and redundant roles in activating the CMG helicase during the replication initiation
AU  - Atabek Bektash
AU  - Xiaoxuan Zhu
AU  - Yuki Hatoyama
AU  - Atsushi Toyoda
AU  - Masato T. Kanemaki
PY  - 2026
DA  - 2026/11/01
PB  - Genes & Development
DO  - 10.1101/gad.353714.126
UR  - https://doi.org/10.1101/gad.353714.126
AB  - 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.
SN  - 0890-9369
SN  - 1549-5477
ER  -