Featured
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Replication stress promotes cell elimination by extrusion
A cell-cycle checkpoint triggers the extrusion of both nematode and mammalian cells experiencing replication stress.
- Vivek K. Dwivedi
- , Carlos Pardo-Pastor
- & H. Robert Horvitz
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AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity
AMBRA1-mediated degradation of cyclin D through CRL4–DDB1 regulates cell proliferation and prevents replication stress in neurodevelopment and cancer.
- Emiliano Maiani
- , Giacomo Milletti
- & Francesco Cecconi
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Securin-independent regulation of separase by checkpoint-induced shugoshin–MAD2
Shugoshin and MAD2 regulate separase-mediated chromosome separation during mitosis, in parallel to a previously identified mechanism involving the anaphase inhibitor securin.
- Susanne Hellmuth
- , Laura Gómez-H
- & Olaf Stemmann
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Separase-triggered apoptosis enforces minimal length of mitosis
If early mitosis is too short, separase induces apoptosis by cleaving MCL2 and BCL-XL, thereby eliminating cells that are prone to chromosome missegregation.
- Susanne Hellmuth
- & Olaf Stemmann
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Letter |
Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13
Structural analysis demonstrates how TRIP13 and p31comet disassemble the mitotic checkpoint complex.
- Claudio Alfieri
- , Leifu Chang
- & David Barford
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Letter |
EMI1 switches from being a substrate to an inhibitor of APC/CCDH1 to start the cell cycle
The transition between early mitotic inhibitor 1 acting as a substrate of the APC/C and as an inhibitor of the same complex results in an irreversible switch that mediates human cell-cycle commitment.
- Steven D. Cappell
- , Kevin G. Mark
- & Tobias Meyer
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Article
| Open AccessThe genome of Schmidtea mediterranea and the evolution of core cellular mechanisms
An improved genome assembly for Schmidtea mediterranea shows that the genome is highly polymorphic and repetitive, and lacks multiple genes encoding core components of cell biological mechanisms.
- Markus Alexander Grohme
- , Siegfried Schloissnig
- & Jochen Christian Rink
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Letter |
Basis of catalytic assembly of the mitotic checkpoint complex
The near-complete in vitro reconstitution of the mitotic spindle assembly checkpoint reveals how the assembly of its effector, the mitotic checkpoint complex, is catalysed.
- Alex C. Faesen
- , Maria Thanasoula
- & Andrea Musacchio
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Molecular basis of APC/C regulation by the spindle assembly checkpoint
A high-resolution structure of a complex between the anaphase-promoting complex (APC/C) and the mitotic checkpoint complex (MCC) reveals how MCC interacts with and represses APC/C by obstructing substrate recognition and suppressing E3 ligase activity.
- Claudio Alfieri
- , Leifu Chang
- & David Barford
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Letter |
Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint
Cell cycle checkpoints, such as the S-phase checkpoint, delay cell division to give the cell time to repair any damaged DNA. Here it is shown that the MLL gene — frequently disrupted in leukaemia — is part of the S-phase checkpoint. When DNA is damaged, MLL is phosphorylated by the ATR protein, causing MLL to accumulate on chromatin and methylate histone H3 on lysine 4. This delays DNA replication. MLL translocations, such as those that occur in leukaemia, disrupt this pathway and cause genomic instability.
- Han Liu
- , Shugaku Takeda
- & James J.-D. Hsieh