Histone synthesis occurs concurrently with DNA replication during the S phase of the cell cycle.
Multiple studies and foundational research confirm that histone synthesis and DNA replication are tightly coupled and occur concurrently during the S phase of the cell cycle to ensure proper chromatin assembly and genomic stability.
The retrieved literature consistently supports the claim that histone synthesis occurs concurrently with DNA replication during the S phase, demonstrating coordination mechanisms and parallel timing.
Xiujie Zhao, Susan McKillop-Smith, Berndt Müller. The human histone gene expression regulator HBP/SLBP is required for histone and DNA synthesis, cell cycle progression and cell proliferation in mitotic cells. 2004. https://doi.org/10.1242/jcs.01523
Paper 2 demonstrates that human HBP/SLBP is essential for the coordinate synthesis of DNA and histone proteins during the cell cycle.
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Angelo M. Delegeane, Amy S. Lee. Coupling of Histone and DNA Synthesis in the Somatic Cell Cycle. 1982. https://doi.org/10.1126/science.7053561
Paper 3 establishes a direct correlation between the rates of DNA and histone synthesis, showing they are coupled.
C. O. Marmolejo, Celina Sanchez, Erin Helms, Melissa J. McEvoy, Juyoung Lee, Marcel Werner, Paige Roberts, Stephan Hamperl, Joshua C. Saldivar. Precise control of transcription condensates across S phase balances linker histone expression with DNA replication, ensuring genome stability. 2026. https://doi.org/10.1016/j.molcel.2026.01.005
Paper 5 details how histone gene expression and transcription condensates are precisely controlled and balanced with DNA replication across the S phase.
A. Dhyani, P. Favaro, S. T. Olalla Saad. ANKHD1 is an S phase protein required for histone synthesis and DNA repair in multiple myeloma cells.. 2020. https://doi.org/10.1016/j.bcmd.2020.102460
Paper 6 notes that histone synthesis occurs in parallel with DNA replication at the S phase.
A. Christopher, H. Hameister, Holly Corrigall, O. Ebenhöh, B. Müller, E. Ullner. Modelling Robust Feedback Control Mechanisms That Ensure Reliable Coordination of Histone Gene Expression with DNA Replication. 2016. https://doi.org/10.1371/journal.pone.0165848
Paper 7 models the robust feedback control mechanisms ensuring the reliable coordination of histone gene expression with DNA replication.
Jiyong Zhao. Coordination of DNA synthesis and histone gene expression during normal cell cycle progression and after DNA damage.. 2004. https://pubmed.ncbi.nlm.nih.gov/15153807/
Paper 9 states that chromosomal DNA replication and histone synthesis are tightly coupled during the S phase of the eukaryotic cell division cycle.
Jacob S Roth, Joseph D DeAngelo, Dejauwne L Young, Maxim I Maron, Ankita Saha, Hugo Pinto, Varun Gupta, Noah Jacobs, Subray Hegde, Jennifer T Aguilan, Joel Basken, Joey Azofeifa, Charles C Query, Simone Sidoli, Arthur I Skoultchi, David Shechter. PRMT5 activity sustains histone production to maintain genome integrity.. 2025. https://doi.org/10.1101/2025.07.03.663002
Paper 11 shows that PRMT5 activity is required to sustain histone transcription and histone protein synthesis during the S phase.
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