Time-Dependent Predominance of Nonhomologous DNA End-Joining Pathways during Embryonic Development in Mice

Chiruvella, Kishore K and Sebastian, Robin and Sharma, Sheetal and Karande, Anjali A and Choudhary, Bibha and Raghavan, Sathees C (2012) Time-Dependent Predominance of Nonhomologous DNA End-Joining Pathways during Embryonic Development in Mice. In: Journal of Molecular Biology, 417 (3). pp. 197-211.

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Abstract

Repair of DNA double-strand breaks (DSBs) is crucial for maintaining genomic integrity during the successful development of a fertilized egg into a whole organism. To date, the mechanism of DSB repair in postimplantation embryos has been largely unknown. In the present study, using a cell-free repair system derived from the different embryonic stages of mice, we find that canonical nonhomologous end joining (NHEJ), one of the major DSB repair pathways in mammals, is predominant at 14.5 day of embryonic development. Interestingly, all four types of DSBs tested were repaired by ligase IV/XRCC4 and Ku-dependent classical NHEJ. Characterization of end-joined junctions and expression studies further showed evidences for canonical NHEJ. Strikingly, in contrast to the above, we observed noncanonical end joining accompanied by DSB resection, dependent on microhomology and ligase III in 18.5-day embryos. Interestingly, we observed an elevated expression of CtIP, MRE11, and NBS1 at this stage, suggesting that it could act as a switch between classical end joining and microhomology-mediated end joining at later stages of embryonic development. Thus, our results establish for the first time the existence of both canonical and alternative NHEJ pathways during the postimplantation stages of mammalian embryonic development. (C) 2012 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Publication:	Journal of Molecular Biology
Publisher:	Elsevier Science
Additional Information:	Copyright of this article belongs to Elsevier Science.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	18 Apr 2012 05:07
Last Modified:	18 Apr 2012 05:07
URI:	http://eprints.iisc.ac.in/id/eprint/44298

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