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Weiß, M. ; Chanou, A. ; Schauer, T. ; Tvardovskiy, A. ; Meiser, S. ; König, A.-C. ; Schmidt, T. ; Kruse, E. ; Ummethum, H. ; Trauner, M. ; Werner, M. ; Lalonde, M. ; Hauck, S.M. ; Scialdone, A. ; Hamperl, S.

Single-copy locus proteomics of early- and late-firing DNA replication origins identifies a role of Ask1/DASH complex in replication timing control.

Cell Rep. 42:112045 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The chromatin environment at origins of replication is thought to influence DNA replication initiation in eukaryotic genomes. However, it remains unclear how and which chromatin features control the firing of early-efficient (EE) or late-inefficient (LI) origins. Here, we use site-specific recombination and single-locus chromatin isolation to purify EE and LI replication origins in Saccharomyces cerevisiae. Using mass spectrometry, we define the protein composition of native chromatin regions surrounding the EE and LI replication start sites. In addition to known origin interactors, we find the microtubule-binding Ask1/DASH complex as an origin-regulating factor. Strikingly, tethering of Ask1 to individual origin sites advances replication timing (RT) of the targeted chromosomal domain. Targeted degradation of Ask1 globally changes RT of a subset of origins, which can be reproduced by inhibiting microtubule dynamics. Thus, our findings mechanistically connect RT and chromosomal organization via Ask1/DASH with the microtubule cytoskeleton.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ask1 Protein ; Cp: Molecular Biology ; Dash Complex ; Dna Replication Origin ; Affinity Purification ; Locus-specific Chromatin Isolation ; Microtubule Cytoskeleton ; Origin Chromatin Structure ; Replication Efficiency ; Replication Timing ; Site-specific Recombination; Kinetochore-microtubule Interface; Yeast; Chromatin; Binding; Recognition; Activation; Initiation; Sequence; Dynamics; Time
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 42, Heft: 2, Seiten: , Artikelnummer: 112045 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epigenetics and Stem Cells (IES)
Institute of Functional Epigenetics (IFE)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Computational Biology (ICB)
POF Topic(s) 30204 - Cell Programming and Repair
30203 - Molecular Targets and Therapies
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Stem Cell and Neuroscience
Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e) G-554500-001
G-506200-001
G-502800-001
G-506290-001
G-505700-001
G-502899-701
G-503800-001
A-630700-001
Förderungen
Helmholtz Gesellschaft
European Research Council (ERC starting grant)
DFG
DOI 10.1016/j.celrep.2023.112045
WOS ID 000961147700001
Scopus ID 85146843974
PubMed ID 36701236
Erfassungsdatum 2023-02-01
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