Phosphorylation of the RecQ Helicase Sgs1/BLM Controls Its DNA Unwinding Activity during Meiosis and Mitosis.


Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
22 06 2020
Historique:
received: 06 12 2019
revised: 18 03 2020
accepted: 13 05 2020
pubmed: 7 6 2020
medline: 2 1 2021
entrez: 7 6 2020
Statut: ppublish

Résumé

The Bloom's helicase ortholog, Sgs1, orchestrates the formation and disengagement of recombination intermediates to enable controlled crossing-over during meiotic and mitotic DNA repair. Whether its enzymatic activity is temporally regulated to implement formation of noncrossovers prior to the activation of crossover-nucleases is unknown. Here, we show that, akin to the Mus81-Mms4, Yen1, and MutLγ-Exo1 nucleases, Sgs1 helicase function is under cell-cycle control through the actions of CDK and Cdc5 kinases. Notably, however, whereas CDK and Cdc5 unleash nuclease function during M phase, they act in concert to stimulate Sgs1 activity during S phase/prophase I. Mechanistically, CDK-mediated phosphorylation enhances the velocity and processivity of Sgs1, which stimulates DNA unwinding in vitro and joint molecule processing in vivo. Subsequent hyper-phosphorylation by Cdc5 appears to reduce the activity of Sgs1, while activating Mus81-Mms4 and MutLγ-Exo1. These findings suggest a concerted mechanism driving orderly formation of noncrossover and crossover recombinants in meiotic and mitotic cells.

Identifiants

pubmed: 32504558
pii: S1534-5807(20)30405-6
doi: 10.1016/j.devcel.2020.05.016
pii:
doi:

Substances chimiques

Cell Cycle Proteins 0
DNA, Fungal 0
Saccharomyces cerevisiae Proteins 0
Protein Serine-Threonine Kinases EC 2.7.11.1
CDC5 protein, S cerevisiae EC 2.7.11.21
SGS1 protein, S cerevisiae EC 3.6.1.-
RecQ Helicases EC 3.6.4.12

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

706-723.e5

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Rokas Grigaitis (R)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.

Lepakshi Ranjha (L)

Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, 6500, Switzerland.

Philipp Wild (P)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.

Kristina Kasaciunaite (K)

Peter Debye Institute for Soft Matter Physics, Universität Leipzig, Leipzig 04103, Germany.

Ilaria Ceppi (I)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, 6500, Switzerland.

Vera Kissling (V)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.

Adrian Henggeler (A)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.

Aitor Susperregui (A)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.

Matthias Peter (M)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.

Ralf Seidel (R)

Peter Debye Institute for Soft Matter Physics, Universität Leipzig, Leipzig 04103, Germany.

Petr Cejka (P)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, 6500, Switzerland.

Joao Matos (J)

Institute of Biochemistry, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland. Electronic address: joao.matos@bc.biol.ethz.ch.

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Classifications MeSH