Proteomic profiling reveals distinct phases to the restoration of chromatin following DNA replication

Vanesa Alvarez, Susanne Bandau, Hao Jiang, Diana Rios-Szwed, Jens Hukelmann, Elisa Garcia-Wilson, Nicola Wiechens, Eva Griesser, Sara Ten Have, Tom Owen-Hughes, Angus Lamond, Constance Alabert (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)
    68 Downloads (Pure)

    Abstract

    Chromatin organization must be maintained during cell proliferation to preserve cellular identity and genome integrity. However, DNA replication results in transient displacement of DNA bound proteins, and it is unclear how they regain access to newly replicated DNA. Using quantitative proteomics coupled to Nascent Chromatin Capture or isolation of Proteins On Nascent DNA, we provide time resolved binding kinetics for thousands of proteins behind replisomes within euchromatin and heterochromatin in human cells. This shows that most proteins regain access within minutes to newly replicated DNA. In contrast, 25% of the identified proteins do not, and this delay cannot be inferred from their known function or nuclear abundance. Instead, chromatin organization and G1 phase entry affect their reassociation. Finally, DNA replication not only disrupts but also promotes recruitment of transcription factors and chromatin remodellers, providing a significant advance in understanding how DNA replication could contribute to programmed changes of cell memory.
    Original languageEnglish
    Article number111996
    Number of pages22
    JournalCell Reports
    Volume42
    Issue number1
    Early online date20 Jan 2023
    DOIs
    Publication statusPublished - 31 Jan 2023

    Keywords

    • Chromatin
    • DNA replication
    • cell cycle
    • propagation
    • restoration
    • euchromatin
    • heterochromatin
    • access to DNA
    • Transcription factors
    • DNA repair
    • Molecular biology

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology

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