Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Cell Biol
2007 Oct 01;2719:6852-62. doi: 10.1128/MCB.00195-07.
Show Gene links
Show Anatomy links
Undamaged DNA transmits and enhances DNA damage checkpoint signals in early embryos.
Peng A
,
Lewellyn AL
,
Maller JL
.
???displayArticle.abstract???
In Xenopus laevis embryos, the midblastula transition (MBT) at the 12th cell division marks initiation of critical developmental events, including zygotic transcription and the abrupt inclusion of gap phases into the cell cycle. Interestingly, although an ionizing radiation-induced checkpoint response is absent in pre-MBT embryos, introduction of a threshold amount of undamaged plasmid or sperm DNA allows a DNA damage checkpoint response to be activated. We show here that undamaged threshold DNA directly participates in checkpoint signaling, as judged by several dynamic changes, including H2AX phosphorylation, ATM phosphorylation and loading onto chromatin, and Chk1/Chk2 phosphorylation and release from nuclear DNA. These responses on physically separate threshold DNA require gamma-H2AX and are triggered by an ATM-dependent soluble signal initiated by damaged DNA. The signal persists in egg extracts even after damaged DNA is removed from the system, indicating that the absence of damaged DNA is not sufficient to end the checkpoint response. The results identify a novel mechanism by which undamaged DNA enhances checkpoint signaling and provide an example of how the transition to cell cycle checkpoint activation during development is accomplished by maternally programmed increases in the DNA-to-cytoplasm ratio.
Anderson,
Ionizing radiation induces apoptosis and elevates cyclin A1-Cdk2 activity before but not after the midblastula transition in Xenopus.
1997, Pubmed,
Xenbase
Anderson,
Ionizing radiation induces apoptosis and elevates cyclin A1-Cdk2 activity before but not after the midblastula transition in Xenopus.
1997,
Pubmed
,
Xenbase
Bakkenist,
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation.
2003,
Pubmed
Bartek,
Chk1 and Chk2 kinases in checkpoint control and cancer.
2003,
Pubmed
Burma,
ATM phosphorylates histone H2AX in response to DNA double-strand breaks.
2001,
Pubmed
Celeste,
Genomic instability in mice lacking histone H2AX.
2002,
Pubmed
Conn,
The DNA damage checkpoint in embryonic cell cycles is dependent on the DNA-to-cytoplasmic ratio.
2004,
Pubmed
,
Xenbase
Costanzo,
Xenopus cell-free extracts to study the DNA damage response.
2004,
Pubmed
,
Xenbase
Dupré,
Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex.
2006,
Pubmed
,
Xenbase
Endean,
Replication of plasmid DNA in fertilized Xenopus eggs is sensitive to both the topology and size of the injected template.
1989,
Pubmed
,
Xenbase
Finkielstein,
The midblastula transition in Xenopus embryos activates multiple pathways to prevent apoptosis in response to DNA damage.
2001,
Pubmed
,
Xenbase
Guo,
Response of Xenopus Cds1 in cell-free extracts to DNA templates with double-stranded ends.
2000,
Pubmed
,
Xenbase
Guo,
Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Han,
Quantitative analysis reveals asynchronous and more than DSB-associated histone H2AX phosphorylation after exposure to ionizing radiation.
2006,
Pubmed
Jazayeri,
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks.
2006,
Pubmed
Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase
Kumagai,
TopBP1 activates the ATR-ATRIP complex.
2006,
Pubmed
,
Xenbase
Li,
DNA damage regulates Chk2 association with chromatin.
2005,
Pubmed
Lukas,
Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage.
2003,
Pubmed
Lupardus,
Phosphorylation of Xenopus Rad1 and Hus1 defines a readout for ATR activation that is independent of Claspin and the Rad9 carboxy terminus.
2006,
Pubmed
,
Xenbase
Maller,
Xenopus oocytes and the biochemistry of cell division.
1990,
Pubmed
,
Xenbase
Marini,
Persistence and replication of plasmid DNA microinjected into early embryos of Xenopus laevis.
1988,
Pubmed
,
Xenbase
Melo,
A unified view of the DNA-damage checkpoint.
2002,
Pubmed
,
Xenbase
Myers,
Rapid activation of ATR by ionizing radiation requires ATM and Mre11.
2006,
Pubmed
Ohi,
Regulating the onset of mitosis.
1999,
Pubmed
,
Xenbase
Paull,
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage.
,
Pubmed
Pellegrini,
Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo.
2006,
Pubmed
Rogakou,
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139.
1998,
Pubmed
Shiloh,
ATM and ATR: networking cellular responses to DNA damage.
2001,
Pubmed
Shiloh,
ATM and related protein kinases: safeguarding genome integrity.
2003,
Pubmed
Smits,
Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response.
2006,
Pubmed
Stucki,
gammaH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes.
2006,
Pubmed
Su,
Cloning and characterization of the Xenopus cyclin-dependent kinase inhibitor p27XIC1.
1995,
Pubmed
,
Xenbase
You,
ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.
2005,
Pubmed
,
Xenbase
Zou,
Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
2003,
Pubmed
