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DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint

DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint
DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint
Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism to prevent the creation of DNA-damaged embryos. Here we show that DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in response to chemically induced double strand breaks, UVB and ionizing radiation. DNA damage can occur either before or after nuclear envelope breakdown, and provides an effective block to anaphase-promoting complex activity, and consequently the formation of mature eggs. This contrasts with somatic cells, where DNA damage fails to affect mitotic progression. However, it uncovers a second function for the meiotic SAC, which in the context of detecting microtubule-kinetochore errors has hitherto been labelled as weak or ineffectual in mammalian oocytes. We propose that its essential role in the detection of DNA damage sheds new light on its biological purpose in mammalian female meiosis.
1-12
Collins, Josie
4547d042-f70c-4563-b1b7-a4bb5e12dbdd
Lane, Simon
8e80111f-5012-4950-a228-dfb8fb9df52d
Merriman-Jones, Julie
252e23f3-b63f-46ed-9904-7986642b4afa
Jones, Keith
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
Collins, Josie
4547d042-f70c-4563-b1b7-a4bb5e12dbdd
Lane, Simon
8e80111f-5012-4950-a228-dfb8fb9df52d
Merriman-Jones, Julie
252e23f3-b63f-46ed-9904-7986642b4afa
Jones, Keith
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4

Collins, Josie, Lane, Simon and Merriman-Jones, Julie et al. (2015) DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint. Nature Communications, 6 (8553), 1-12. (doi:10.1038/ncomms9553). (PMID:26522232)

Record type: Article

Abstract

Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism to prevent the creation of DNA-damaged embryos. Here we show that DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in response to chemically induced double strand breaks, UVB and ionizing radiation. DNA damage can occur either before or after nuclear envelope breakdown, and provides an effective block to anaphase-promoting complex activity, and consequently the formation of mature eggs. This contrasts with somatic cells, where DNA damage fails to affect mitotic progression. However, it uncovers a second function for the meiotic SAC, which in the context of detecting microtubule-kinetochore errors has hitherto been labelled as weak or ineffectual in mammalian oocytes. We propose that its essential role in the detection of DNA damage sheds new light on its biological purpose in mammalian female meiosis.

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Published date: 2 November 2015
Organisations: Biomedicine

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Local EPrints ID: 383430
URI: https://eprints.soton.ac.uk/id/eprint/383430
PURE UUID: 127bad61-e83c-46df-8272-84d7d23b9aaa
ORCID for Simon Lane: ORCID iD orcid.org/0000-0002-8155-0981
ORCID for Keith Jones: ORCID iD orcid.org/0000-0002-0294-0851

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Date deposited: 30 Nov 2015 10:20
Last modified: 07 Aug 2019 00:34

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Contributors

Author: Josie Collins
Author: Simon Lane ORCID iD
Author: Julie Merriman-Jones
Author: Keith Jones ORCID iD

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