Molecular control of replication licensing speed by c-MYC
- 1University of North Carolina at Chapel Hill
Abstract
A critical prerequisite for DNA replication is genome-wide origin licensing, a process tightly restricted to the G1 cell cycle phase. This restriction means that short G1 cells must license quickly or risk incomplete replication and genome instability, but mechanisms to increase licensing speed are largely unknown. Using quantitative single cell approaches, we identify here a non-canonical role for c-MYC as a potent origin licensing accelerator. Importantly, a point mutation separates c-MYC-induced rapid licensing from the well-known c-MYC gene expression function. c-MYC accelerates licensing through the TRRAP lysine acetyltransferase adapter and GCN5 acetyltransferase. In addition c-MYC has the unexpected ability to induce widespread linker histone H1 eviction. Moreover, directly reducing chromatin-bound histone H1 is sufficient to accelerate licensing. In addition, c-MYC stimulates licensing in heterochromatin, a typically slow-licensing genome compartment. We suggest that global chromatin opening promotes rapid licensing when G1 phase is short such as during early development, rapid progenitor cell proliferation, and adaptation to oncogene activation.
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BibTeX
@misc{fleifel2026molecular,
title = {{Molecular control of replication licensing speed by c-MYC}},
author = {D. Fleifel and A. Khan and A. A. Alkhawaja and A. Adavikolanu and S. Qayyum and E. Elkoumy and J. G. Cook},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762773},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762773v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Molecular control of replication licensing speed by c-MYC
AU - D. Fleifel
AU - A. Khan
AU - A. A. Alkhawaja
AU - A. Adavikolanu
AU - S. Qayyum
AU - E. Elkoumy
AU - J. G. Cook
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762773
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762773v1
AB - A critical prerequisite for DNA replication is genome-wide origin licensing, a process tightly restricted to the G1 cell cycle phase. This restriction means that short G1 cells must license quickly or risk incomplete replication and genome instability, but mechanisms to increase licensing speed are largely unknown. Using quantitative single cell approaches, we identify here a non-canonical role for c-MYC as a potent origin licensing accelerator. Importantly, a point mutation separates c-MYC-induced rapid licensing from the well-known c-MYC gene expression function. c-MYC accelerates licensing through the TRRAP lysine acetyltransferase adapter and GCN5 acetyltransferase. In addition c-MYC has the unexpected ability to induce widespread linker histone H1 eviction. Moreover, directly reducing chromatin-bound histone H1 is sufficient to accelerate licensing. In addition, c-MYC stimulates licensing in heterochromatin, a typically slow-licensing genome compartment. We suggest that global chromatin opening promotes rapid licensing when G1 phase is short such as during early development, rapid progenitor cell proliferation, and adaptation to oncogene activation.
ER -