The Fission Yeast Crb2/Chk1 Pathway Coordinates the DNA Damage and Spindle Checkpoint in Response to Replication Stress Induced by Topoisomerase I Inhibitor - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Molecular and Cellular Biology Année : 2005

The Fission Yeast Crb2/Chk1 Pathway Coordinates the DNA Damage and Spindle Checkpoint in Response to Replication Stress Induced by Topoisomerase I Inhibitor

Ada Collura
  • Fonction : Auteur
Joel Blaisonneau
  • Fonction : Auteur
Giuseppe Baldacci
  • Fonction : Auteur

Résumé

Living organisms experience constant threats that challenge their genome stability. The DNA damage checkpoint pathway coordinates cell cycle progression with DNA repair when DNA is damaged, thus ensuring faithful transmission of the genome. The spindle assembly checkpoint inhibits chromosome segregation until all chromosomes are properly attached to the spindle, ensuring accurate partition of the genetic material. Both the DNA damage and spindle checkpoint pathways participate in genome integrity. However, no clear connection between these two pathways has been described. Here, we analyze mutants in the BRCT domains of fission yeast Crb2, which mediates Chk1 activation, and provide evidence for a novel function of the Chk1 pathway. When the Crb2 mutants experience damaged replication forks upon inhibition of the religation activity of topoisomerase I, the Chk1 DNA damage pathway induces sustained activation of the spindle checkpoint, which in turn delays metaphase-to-anaphase transition in a Mad2-dependent fashion. This new pathway enhances cell survival and genome stability when cells undergo replicative stress in the absence of a proficient G(2)/M DNA damage checkpoint.

Dates et versions

hal-03008088 , version 1 (16-11-2020)

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Ada Collura, Joel Blaisonneau, Giuseppe Baldacci, Stefania Francesconi. The Fission Yeast Crb2/Chk1 Pathway Coordinates the DNA Damage and Spindle Checkpoint in Response to Replication Stress Induced by Topoisomerase I Inhibitor. Molecular and Cellular Biology, 2005, 25 (17), pp.7889-7899. ⟨10.1128/MCB.25.17.7889-7899.2005⟩. ⟨hal-03008088⟩

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