2022年6月
Mre11 exonuclease activity promotes irreversible mitotic progression under replication stress
Life Science Alliance
- ,
- 巻
- 5
- 号
- 6
- 開始ページ
- e202101249
- 終了ページ
- e202101249
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.26508/lsa.202101249
- 出版者・発行元
- Life Science Alliance, LLC
Mre11 is a versatile exo-/endonuclease involved in multiple aspects of DNA replication and repair, such as DSB end processing and checkpoint activation. We previously demonstrated that forced mitotic entry drives replisome disassembly at stalled replication forks in Xenopus egg extracts. Here, we examined the effects of various chemical inhibitors using this system and discovered a novel role of Mre11 exonuclease activity in promoting mitotic entry under replication stress. Mre11 activity was necessary for the initial progression of mitotic entry in the presence of stalled forks but unnecessary in the absence of stalled forks or after mitotic entry. In the absence of Mre11 activity, mitotic CDK was inactivated by Wee1/Myt1–dependent phosphorylation, causing mitotic exit. An inhibitor of Wee1/Myt1 or a nonphosphorylatable CDK1 mutant was able to partially bypass the requirement of Mre11 for mitotic entry. These results suggest that Mre11 exonuclease activity facilitates the processing of stalled replication forks upon mitotic entry, which attenuates the inhibitory pathways of mitotic CDK activation, leading to irreversible mitotic progression and replisome disassembly.
- リンク情報
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- DOI
- https://doi.org/10.26508/lsa.202101249
- 共同研究・競争的資金等の研究課題
- 分裂期レプリソーム脱離機構の解明
- 共同研究・競争的資金等の研究課題
- 複製フォーク崩壊過程におけるレプリソーム動態制御
- URL
- https://syndication.highwire.org/content/doi/10.26508/lsa.202101249
- ID情報
-
- DOI : 10.26508/lsa.202101249
- eISSN : 2575-1077