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Marmolejo, C.O.* ; Sanchez, C.* ; Helms, E.* ; McEvoy, M.J.* ; Lee, J.* ; Werner, M. ; Roberts, P.* ; Hamperl, S. ; Saldivar, J.C.*

Precise control of transcription condensates across S phase balances linker histone expression with DNA replication, ensuring genome stability.

Mol. Cell 86, 640-655.e6 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Transcription condensates are liquid-like compartments where transcription factors, co-activators, and RNA polymerases are selectively enriched and regulate transcription initiation of associated genes. While the principles governing the enrichment of proteins within transcription condensates are being elucidated, mechanisms that coordinate condensate dynamics with other nuclear processes, such as DNA replication, have not been identified. We show in human cells that at the G1/S cell-cycle transition, large transcription condensates form at histone locus bodies (HLBs) in a cyclin-dependent kinase 1 and 2 (CDK1/2)-dependent manner. By mid-S phase, ataxia-telangiectasia and Rad3-related kinase (ATR) accumulates within HLBs and dissolves the associated condensates via its downstream effector, CHK1. Failure to dissolve condensates results in overexpression of linker H1 histones and nucleus-wide DNA damage. Moreover, an imbalance in the different linker histones accentuates DNA damage in ATR-CHK1-deficient cells. Our work reveals how transcription condensates are precisely controlled in the S phase to fine-tune gene activation and safeguard genome stability.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Atr ; Dna Damage ; Med1 ; Genome Stability ; Histone Locus Body ; Linker Histones ; Transcription Condensates; Cyclin E-cdk2; Atr; Disruption; Separation; Lethality; Distinct; Damage; Leads; Npat
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Journal Molecular Cell
Quellenangaben Volume: 86, Issue: 4, Pages: 640-655.e6 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)
Grants Office of Research Infrastructure Programs, Office of the Director, NIH
American Association for Cancer Research (AACR)
CEDAR, an NIH
European Research Council (ERC)
German Research Foundation (DFG)
Helmholtz Association
National Institutes of Health (NIH)
Cancer Early Detection Advanced Research Center (CEDAR)