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Checkpoint for DNA integrity at the first mitosis after oocyte activation

Checkpoint for DNA integrity at the first mitosis after oocyte activation
Checkpoint for DNA integrity at the first mitosis after oocyte activation
Activation of oocytes, arrested at the meiosis II (MII) in mammals, initiates meiotic release, mitotic divisions, and development. Unlike most somatic cell types, MII arrested female germ cells lack an efficient DNA integrity checkpoint control. Here we present evidence showing a unique checkpoint for DNA integrity at first mitosis after oocyte activation. Mouse oocytes carrying intact DNA cleaved normally after meiotic release, whereas 50% of oocytes harboring damaged DNA manifested cytofragmentation, a morphological hallmark of apoptosis. If not activated, DNA-damaged MII oocytes did not show apoptotic fragmentation. Further, activated, enucleated oocytes or enucleated fertilized oocytes also underwent cytofragmentation, implicating cytoplasmic coordination of the fragmentation process, independent of the nucleus. Depolymerization of either actin filaments or microtubules induced no cytofragmentation, but inhibited fragmentation upon oocyte activation. During the process of fragmentation, microtubule networks formed, then microtubule asters congregated at discrete locations, around which fragmented cellular bodies formed. Mitotic spindles, however, were not formed inactivated oocytes with damaged or absent DNA; in contrast, normal mitotic spindles were formed in activated oocytes with intact DNA. These results demonstrate that damaged DNA or absence of DNA leads to cytofragmentation after oocyte activation. Further, we found a mechanism of cytoskeletal involvement in the process of cytofragmentation. In addition, possible implication of the present findings in somatic cell cloning and human clinical embryology is discussed. Mol. Reprod. Dev. 62: 277–288, 2002. © 2002 Wiley-Liss, Inc.

dna checkpoint, first mitosis, dna damage, cytofragmentation, oocyte activation
1040-452X
277-288
Liu, Lin
51bc0635-5ce3-4ade-9edf-624ec8a1750b
Trimarchi, James R.
dc15c269-2b07-41fb-b3e5-a9ac457c7994
Smith, Peter J.S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Keefe, David L.
a1d0a08b-d76a-4d64-b2dd-4d1a5fc04451
Liu, Lin
51bc0635-5ce3-4ade-9edf-624ec8a1750b
Trimarchi, James R.
dc15c269-2b07-41fb-b3e5-a9ac457c7994
Smith, Peter J.S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Keefe, David L.
a1d0a08b-d76a-4d64-b2dd-4d1a5fc04451

Liu, Lin, Trimarchi, James R., Smith, Peter J.S. and Keefe, David L. (2002) Checkpoint for DNA integrity at the first mitosis after oocyte activation. Molecular Reproduction and Development, 62 (2), 277-288. (doi:10.1002/mrd.10094). (PMID:11984839)

Record type: Article

Abstract

Activation of oocytes, arrested at the meiosis II (MII) in mammals, initiates meiotic release, mitotic divisions, and development. Unlike most somatic cell types, MII arrested female germ cells lack an efficient DNA integrity checkpoint control. Here we present evidence showing a unique checkpoint for DNA integrity at first mitosis after oocyte activation. Mouse oocytes carrying intact DNA cleaved normally after meiotic release, whereas 50% of oocytes harboring damaged DNA manifested cytofragmentation, a morphological hallmark of apoptosis. If not activated, DNA-damaged MII oocytes did not show apoptotic fragmentation. Further, activated, enucleated oocytes or enucleated fertilized oocytes also underwent cytofragmentation, implicating cytoplasmic coordination of the fragmentation process, independent of the nucleus. Depolymerization of either actin filaments or microtubules induced no cytofragmentation, but inhibited fragmentation upon oocyte activation. During the process of fragmentation, microtubule networks formed, then microtubule asters congregated at discrete locations, around which fragmented cellular bodies formed. Mitotic spindles, however, were not formed inactivated oocytes with damaged or absent DNA; in contrast, normal mitotic spindles were formed in activated oocytes with intact DNA. These results demonstrate that damaged DNA or absence of DNA leads to cytofragmentation after oocyte activation. Further, we found a mechanism of cytoskeletal involvement in the process of cytofragmentation. In addition, possible implication of the present findings in somatic cell cloning and human clinical embryology is discussed. Mol. Reprod. Dev. 62: 277–288, 2002. © 2002 Wiley-Liss, Inc.

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More information

Published date: June 2002
Keywords: dna checkpoint, first mitosis, dna damage, cytofragmentation, oocyte activation

Identifiers

Local EPrints ID: 188839
URI: http://eprints.soton.ac.uk/id/eprint/188839
ISSN: 1040-452X
PURE UUID: 9874dea3-4f13-4876-82c2-dbd81cdf1d69
ORCID for Peter J.S. Smith: ORCID iD orcid.org/0000-0003-4400-6853

Catalogue record

Date deposited: 13 Jun 2011 13:39
Last modified: 21 Nov 2021 03:04

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Contributors

Author: Lin Liu
Author: James R. Trimarchi
Author: David L. Keefe

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