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Spatial control of the GEN1 Holliday junction resolvase ensures genome stability

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  • Ying Wai Chan

    (London Research Institute, Cancer Research UK, Clare Hall Laboratories)

  • Stephen C. West

    (London Research Institute, Cancer Research UK, Clare Hall Laboratories)

Abstract

Holliday junction (HJ) resolvases are necessary for the processing of persistent recombination intermediates before cell division. Their actions, however, need to be restricted to the late stages of the cell cycle to avoid the inappropriate cleavage of replication intermediates. Control of the yeast HJ resolvase, Yen1, involves phosphorylation changes that modulate its catalytic activity and nuclear import. Here, we show that GEN1, the human ortholog of Yen1, is regulated by a different mechanism that is independent of phosphorylation. GEN1 is controlled exclusively by nuclear exclusion, driven by a nuclear export signal (NES) that restricts GEN1 actions to mitosis when the nuclear membrane breaks down. Construction of a nuclear-localized version of GEN1 revealed that its premature actions partially suppress phenotypes associated with loss of BLM and MUS81, but cause elevated crossover formation. The spatial control of GEN1 therefore contributes to genome stability, by avoiding competition with non-crossover promoting repair pathways.

Suggested Citation

  • Ying Wai Chan & Stephen C. West, 2014. "Spatial control of the GEN1 Holliday junction resolvase ensures genome stability," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5844
    DOI: 10.1038/ncomms5844
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    1. Anne Margriet Heijink & Colin Stok & David Porubsky & Eleni Maria Manolika & Jurrian K. Kanter & Yannick P. Kok & Marieke Everts & H. Rudolf Boer & Anastasia Audrey & Femke J. Bakker & Elles Wierenga , 2022. "Sister chromatid exchanges induced by perturbed replication can form independently of BRCA1, BRCA2 and RAD51," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Mara De Marco Zompit & Mònica Torres Esteban & Clémence Mooser & Salomé Adam & Silvia Emma Rossi & Alain Jeanrenaud & Pia-Amata Leimbacher & Daniel Fink & Ann-Marie K. Shorrocks & Andrew N. Blackford , 2022. "The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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