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Molecular and Cellular Biology, October 2007, p. 6852-6862, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.00195-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Undamaged DNA Transmits and Enhances DNA Damage Checkpoint Signals in Early Embryos{triangledown}

Aimin Peng, Andrea L. Lewellyn, and James L. Maller*

Howard Hughes Medical Institute and Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045

Received 1 February 2007/ Returned for modification 5 March 2007/ Accepted 18 July 2007

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.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Mail Stop F-8303, Department of Pharmacology, University of Colorado School of Medicine, RC-1 South, Room L18-10124, 12801 E. 17th Avenue, P.O. Box 6511, Aurora, CO 80045. Phone: (303) 724-1623. Fax: (303) 724-1626. E-mail: jim.maller{at}uchsc.edu

{triangledown} Published ahead of print on 30 July 2007.

Molecular and Cellular Biology, October 2007, p. 6852-6862, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.00195-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Collart, C., Ramis, J. M., Down, T. A., Smith, J. C. (2009). Smicl is required for phosphorylation of RNA polymerase II and affects 3'-end processing of RNA at the midblastula transition in Xenopus. Development 136: 3451-3461 [Abstract] [Full Text]  


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