Evolutionary conservation of a novel splice variant of the Cds1/CHK2 checkpoint kinase restricted to its regulatory domain.

Matthieu Lemaire (1) , Joanna Prime (1) , Bernard Ducommun (1) , Béatrix Bugler (1)

1 LBCMCP - Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération

The Cds1/CHK2 kinase plays a key role in the activation of the G(2) checkpoint after DNA damage. Here we report the existence in fission yeast of a short variant (Sv) of Cds1 that is produced through an alternative splicing mechanism leading to a frame shift and premature termination. This SvCds1 protein consists solely of the regulatory region and lacks the catalytic domain. Expression of SvCds1 increases sensitivity to ionizing radiation and, to a lesser extent, to hydroxyurea, but not to UV radiation. We also report that in the human orthologue of Cds1, CHK2, differential splicing of a cryptic exon leads to a frame shift and premature termination producing a short variant (SvCHK2). Thus, we have discovered the existence of an evolutionary conserved mechanism ensuring the production of a catalytically inactive variant Cds1/CHK2 that is restricted to SQTQ and FHA domains and that can act as a dominant negative. The role that this short variant of Cds1/CHK2 might play in the response to DNA damage and the physiopathological consequences are discussed.

Domaines: Biologie cellulaire

Matthieu Lemaire, Joanna Prime, Bernard Ducommun, Béatrix Bugler. Evolutionary conservation of a novel splice variant of the Cds1/CHK2 checkpoint kinase restricted to its regulatory domain.. Cell Cycle, 2004, 3 (10), pp.1267-70. ⟨10.4161/cc.3.10.1154⟩. ⟨hal-00317436⟩