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DNA damage responses in mammalian oocytes

DNA damage responses in mammalian oocytes
DNA damage responses in mammalian oocytes
DNA damage acquired during meiosis can lead to infertility and miscarriage. Hence it should be important for an oocyte to be able to detect and respond to such events in order to make a healthy egg. Here the strategies taken by oocytes during their stages of growth to respond to DNA damaging events are reviewed. In particular, recent evidence of a novel pathway in fully grown oocyte that helps prevent the formation of mature eggs with DNA damage. It has been found that fully grown germinal vesicle stage oocytes that have been DNA damaged do not arrest at this point in meiosis, but instead undergo meiotic resumption and stall during the first meiotic division. The Spindle Assembly Checkpoint, which is a well-known mitotic pathway employed by somatic cells to monitor chromosome attachment to spindle microtubules, appears to be utilised by oocytes also to respond to DNA damage. As such, maturing oocytes arrest at metaphase I, due to an active Spindle Assembly Checkpoint. This is surprising given this checkpoint has been previously studied in oocytes and thought to be weak and ineffectual because of its poor ability to be activated in response to microtubule attachment errors. Therefore the involvement of the Spindle Assembly Checkpoint in DNA damage responses of mature oocytes during meiosis I, uncovers a novel second function for this ubiquitous cellular checkpoint.
0022-4251
R15-R22
Collins, J.K
4547d042-f70c-4563-b1b7-a4bb5e12dbdd
Jones, K.T
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
Collins, J.K
4547d042-f70c-4563-b1b7-a4bb5e12dbdd
Jones, K.T
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4

Collins, J.K and Jones, K.T (2016) DNA damage responses in mammalian oocytes. Reproduction, 152 (1), R15-R22. (doi:10.1530/REP-16-0069).

Record type: Review

Abstract

DNA damage acquired during meiosis can lead to infertility and miscarriage. Hence it should be important for an oocyte to be able to detect and respond to such events in order to make a healthy egg. Here the strategies taken by oocytes during their stages of growth to respond to DNA damaging events are reviewed. In particular, recent evidence of a novel pathway in fully grown oocyte that helps prevent the formation of mature eggs with DNA damage. It has been found that fully grown germinal vesicle stage oocytes that have been DNA damaged do not arrest at this point in meiosis, but instead undergo meiotic resumption and stall during the first meiotic division. The Spindle Assembly Checkpoint, which is a well-known mitotic pathway employed by somatic cells to monitor chromosome attachment to spindle microtubules, appears to be utilised by oocytes also to respond to DNA damage. As such, maturing oocytes arrest at metaphase I, due to an active Spindle Assembly Checkpoint. This is surprising given this checkpoint has been previously studied in oocytes and thought to be weak and ineffectual because of its poor ability to be activated in response to microtubule attachment errors. Therefore the involvement of the Spindle Assembly Checkpoint in DNA damage responses of mature oocytes during meiosis I, uncovers a novel second function for this ubiquitous cellular checkpoint.

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Reproduction_AM_eprints.pdf - Accepted Manuscript
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More information

Accepted/In Press date: 7 April 2016
e-pub ahead of print date: 11 April 2016
Published date: July 2016
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 391974
URI: http://eprints.soton.ac.uk/id/eprint/391974
ISSN: 0022-4251
PURE UUID: 2c2434de-d8e7-4495-85c0-f2b6c8dc7a7b
ORCID for K.T Jones: ORCID iD orcid.org/0000-0002-0294-0851

Catalogue record

Date deposited: 12 Apr 2016 15:29
Last modified: 17 Dec 2019 06:52

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