ArticleMolecular biology of the cell2003
DNA damage during the spindle-assembly checkpoint degrades CDC25A, inhibits cyclin-CDC2 complexes, and reverses cells to interphase.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 50 citations in OpenAlex.
- Premature activation of Cdk1 leads to mitotic events in S phase and embryonic lethality.Oncogene · 2019Article
- Maintaining Genome Stability in Defiance of Mitotic DNA Damage.Frontiers in genetics · 2016Review
- Role of RUNX2 in Breast Carcinogenesis.International journal of molecular sciences · 2015Review
- Co-inhibition of polo-like kinase 1 and Aurora kinases promotes mitotic catastrophe.Oncotarget · 2015Article
- DNA damage to a single chromosome end delays anaphase onset.The Journal of biological chemistry · 2014Article
- CHK1 inhibitors in combination chemotherapy: thinking beyond the cell cycle.Molecular interventions · 2011Review
- In vitro gene regulatory networks predict in vivo function of liver.BMC systems biology · 2010Article
- Avian reovirus nonstructural protein p17-induced G(2)/M cell cycle arrest and host cellular protein translation shutoff involve activation of p53-dependent pathways.Journal of virology · 2010Article
- Depression of MAD2 inhibits apoptosis and increases proliferation and multidrug resistance in gastric cancer cells by regulating the activation of phosphorylated survivin.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2010Article
- Generation of an indestructible cyclin B1 by caspase-6-dependent cleavage during mitotic catastrophe.Oncogene · 2009Article
- RPA phosphorylation facilitates mitotic exit in response to mitotic DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Specialized roles of the two mitotic cyclins in somatic cells: cyclin A as an activator of M phase-promoting factor.Molecular biology of the cell · 2007Article
- Downregulation of Fer induces PP1 activation and cell-cycle arrest in malignant cells.Oncogene · 2006Article
- How many mutant p53 molecules are needed to inactivate a tetramer?Molecular and cellular biology · 2004Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell cycle checkpoints that monitor DNA damage and spindle assembly are essential for the maintenance of genetic integrity, and drugs that target these checkpoints are important chemotherapeutic agents. We have examined how cells respond to DNA damage while the spindle-assembly checkpoint is activated. Single cell electrophoresis and phosphorylation of histone H2AX indicated that several chemotherapeutic agents could induce DNA damage during mitotic block. DNA damage during mitotic block triggered CDC2 inactivation, histone H3 dephosphorylation, and chromosome decondensation. Cells did not progress into G1 but seemed to retract to a G2-like state containing 4N DNA content, with stabilized cyclin A and cyclin B1 binding to Thr14/Tyr15-phosphorylated CDC2. The loss of mitotic cells was not due to cell death because there was no discernible effect on caspase-3 activation, DNA fragmentation, or viability. Extensive DNA damage during mitotic block inactivated cyclin B1-CDC2 and prevented G1 entry when the block was removed. The mitotic DNA damage responses were independent of p53 and pRb, but they were dependent on ATM. CDC25A that accumulated during mitosis was rapidly destroyed after DNA damage in an ATM-dependent manner. Ectopic expression of CDC25A or nonphosphorylatable CDC2 effectively inhibited the dephosphorylation of histone H3 after DNA damage. Hence, although spindle disruption and DNA damage provide conflicting signals to regulate CDC2, the negative regulation by the DNA damage checkpoint could overcome the positive regulation by the spindle-assembly checkpoint.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.