Translator Disclaimer
3 May 2018 WIP1 phosphatase suppresses the DNA damage response during G2/prophase arrest in mouse oocytes
Jiyeon Leem, Jae-Sung Kim, Jeong Su Oh
Author Affiliations +
Abstract

Maternal DNA damage duringmeiosis causes genetic abnormalities that can lead to infertility, birth defects, and abortion. While DNA damage can rapidly halt cell cycle progression and promote DNA repair in somatic cells, mammalian oocytes are unable to mount a robust G2/prophase arrest in response to DNA damage unless damage levels are severe. Here, we show that inhibition of WIP1 phosphatase enhances the ability of oocytes to respond to DNA damage. We found that WIP1 was expressed constantly during meiotic maturation, and that inhibition of WIP1 activity did not impair meiotic maturation. However, oocytes in G2/prophase were sensitized to DNA damage following WIP1 inhibition, not only increasing γ -H2AX level and ATM phosphorylation, but also decreasing entry into meiosis. Moreover, WIP1 inhibition significantly promoted the repair of damaged DNA during G2/prophase arrest, suggesting thatWIP1 suppresses DNA repair in oocytes. Therefore, our results suggest that WIP1 is a key suppressor of the DNA damage response during G2/prophase arrest in mouse oocytes.

Summary Sentence

Inhibition of WIP1 phosphatase sensitizes mouse oocytes to DNA damage and improves the ability of oocytes to repair DNA damage.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Jiyeon Leem, Jae-Sung Kim, and Jeong Su Oh "WIP1 phosphatase suppresses the DNA damage response during G2/prophase arrest in mouse oocytes," Biology of Reproduction 99(4), 798-805, (3 May 2018). https://doi.org/10.1093/biolre/ioy108
Received: 5 January 2018; Accepted: 30 April 2018; Published: 3 May 2018
JOURNAL ARTICLE
8 PAGES


Share
SHARE
KEYWORDS
DNA damage
DNA repair
meiotic resumption
WIP1 phosphatase
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top