Faculty Opinions recommendation of Developmental control of late replication and S phase length.

During metazoan development, the cell cycle is remodelled to coordinate proliferation with differentiation. Developmental cues cause dramatic changes in the number and timing of replication initiation events, but the mechanisms and physiological importance of such changes are poorly understood. Cyclin-dependent kinases (CDKs) are important for regulating S-phase length in many metazoa, and here we show in the nematode Caenorhabditis elegans that an essential function of CDKs during early embryogenesis is to regulate the interactions between three replication initiation factors SLD-3, SLD-2 and MUS-101 (Dpb11/TopBP1). Mutations that bypass the requirement for CDKs to generate interactions between these factors is partly sufficient for viability in the absence of Cyclin E, demonstrating that this is a critical embryonic function of this Cyclin. Both SLD-2 and SLD-3 are asymmetrically localised in the early embryo and the levels of these proteins inversely correlate with S-phase length. We also show that SLD-2 asymmetry is determined by direct interaction with the polarity protein PKC-3. This study explains an essential function of CDKs for replication initiation in a metazoan and provides the first direct molecular mechanism through which polarization of the embryo is coordinated with DNA replication initiation factors.

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Acute effects of wheel running on adult hippocampal precursor cells in mice are not caused by changes in cell cycle length or S phase length

Frontiers in Neuroscience ◽

10.3389/fnins.2014.00314 ◽

2014 ◽

Vol 8 ◽

Cited By ~ 20

Author(s):

Tim J. Fischer ◽

Tara L. Walker ◽

Rupert W. Overall ◽

Moritz D. Brandt ◽

Gerd Kempermann

Keyword(s):

Cell Cycle ◽

Cycle Length ◽

Wheel Running ◽

Precursor Cells ◽

S Phase ◽

Acute Effects ◽

Cell Cycle Length ◽

Phase Length

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Uncoupling global and fine-tuning replication timing determinants for mouse pericentric heterochromatin

The Journal of Cell Biology ◽

10.1083/jcb.200601113 ◽

2006 ◽

Vol 174 (2) ◽

pp. 185-194 ◽

Cited By ~ 40

Author(s):

Rong Wu ◽

Prim B. Singh ◽

David M. Gilbert

Keyword(s):

Replication Timing ◽

Pericentric Heterochromatin ◽

S Phase ◽

Fine Tuning ◽

G1 Phase ◽

Late Replication ◽

Free System ◽

Replication Time ◽

A Cell ◽

Early Replication

Mouse chromocenters are clusters of late-replicating pericentric heterochromatin containing HP1 bound to trimethylated lysine 9 of histone H3 (Me3K9H3). Using a cell-free system to initiate replication within G1-phase nuclei, we demonstrate that chromocenters acquire the property of late replication coincident with their reorganization after mitosis and the establishment of a global replication timing program. HP1 dissociated during mitosis but rebound before the establishment of late replication, and removing HP1 from chromocenters by competition with Me3K9H3 peptides did not result in early replication, demonstrating that this interaction is neither necessary nor sufficient for late replication. However, in cells lacking the Suv39h1,2 methyltransferases responsible for K9H3 trimethylation and HP1 binding at chromocenters, replication of chromocenter DNA was advanced by 10–15% of the length of S phase. Reintroduction of Suv39h1 activity restored the later replication time. We conclude that Suv39 activity is required for the fine-tuning of pericentric heterochromatin replication relative to other late-replicating domains, whereas separate factors establish a global replication timing program during early G1 phase.

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Ensa controls S-phase length by modulating Treslin levels

Nature Communications ◽

10.1038/s41467-017-00339-4 ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 23

Author(s):

Sophie Charrasse ◽

Aicha Gharbi-Ayachi ◽

Andrew Burgess ◽

Jorge Vera ◽

Khaled Hached ◽

...

Keyword(s):

S Phase ◽

Phase Length

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Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p

Genes & Development ◽

10.1101/gad.14.4.493 ◽

2000 ◽

Vol 14 (4) ◽

pp. 493-503 ◽

Cited By ~ 2

Author(s):

Rita S. Cha ◽

Beth M. Weiner ◽

Scott Keeney ◽

Job Dekker ◽

N. Kleckner

Keyword(s):

Dna Replication ◽

Phase Modulation ◽

Cell Types ◽

Strand Break ◽

S Phase ◽

Wild Type ◽

Homolog Pairing ◽

Defective Mutant ◽

Phase Progression ◽

Phase Length

Spo11p is a key mediator of interhomolog interactions during meiosis. Deletion of the SPO11 gene decreases the length of S phase by ∼25%. Rec8p is a key coordinator of meiotic interhomolog and intersister interactions. Deletion of the REC8 gene increases S-phase length, by ∼10% in wild-type and ∼30% in aspo11Δ background. Thus, the progression of DNA replication is modulated by interchromosomal interaction proteins. Thespo11–Y135F DSB (double strand break) catalysis-defective mutant is normal for S-phase modulation and DSB-independent homolog pairing but is defective for later events, formation of DSBs, and synaptonemal complexes. Thus, earlier and later functions of Spo11 are defined. We propose that meiotic S-phase progression is linked directly to development of specific chromosomal features required for meiotic interhomolog interactions and that this feedback process is built upon a more fundamental mechanism, common to all cell types, by which S-phase progression is coupled to development of nascent intersister connections and/or related aspects of chromosome morphogenesis. Roles for Rec8 and/or Spo11 in progression through other stages of meiosis are also revealed.

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Faculty Opinions recommendation of E2F-dependent transcription determines replication capacity and S phase length.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738321006.793576655 ◽

2020 ◽

Author(s):

Jean Cook

Keyword(s):

S Phase ◽

Replication Capacity ◽

Phase Length

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E2F-dependent transcription determines replication capacity and S phase length

Nature Communications ◽

10.1038/s41467-020-17146-z ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Betheney R. Pennycook ◽

Eva Vesela ◽

Silvia Peripolli ◽

Tanya Singh ◽

Alexis R. Barr ◽

...

Keyword(s):

S Phase ◽

Replication Capacity ◽

Phase Length

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Identification of two telomere-proximal fission yeast DNA replication origins constrained by nearby cis-acting sequences to replicate in late S phase

F1000Research ◽

10.12688/f1000research.1-58.v1 ◽

2012 ◽

Vol 1 ◽

pp. 58 ◽

Cited By ~ 2

Author(s):

Amna Chaudari ◽

Joel A Huberman

Keyword(s):

Dna Replication ◽

Fission Yeast ◽

S Phase ◽

Yeast Genome ◽

Late Replication ◽

Replication Origins ◽

Replication Checkpoint ◽

Cis Acting ◽

Associated Sequences ◽

Dna Replication Origins

Telomeres of the fission yeast, Schizosaccharomyces pombe, are known to replicate in late S phase, but the reasons for this late replication are not fully understood. We have identified two closely-spaced DNA replication origins, 5.5 to 8 kb upstream from the telomere itself. These are the most telomere-proximal of all the replication origins in the fission yeast genome. When located by themselves in circular plasmids, these origins fired in early S phase, but if flanking sequences closer to the telomere were included in the circular plasmid, then replication was restrained to late S phase – except in cells lacking the replication-checkpoint kinase, Cds1. We conclude that checkpoint-dependent late replication of telomere-associated sequences is dependent on nearby cis-acting sequences, not on proximity to the physical end of a linear chromosome.

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