Conserved ATRMec1 phosphorylation-independent activation of Chk1 by single amino acid substitution in the GD domain.

ABSTRACT: Chk1 is a conserved kinase that comprises the first line of defense against DNA damage and replication blocks. Chk1 consists of two primary domains, the well conserved N-terminal kinase domain and the non-catalytic C-terminal domain that contains the two highly conserved TRF and GD sub-domains. Several studies suggested that the C-terminus of Chk1 acts as an inhibitory domain and that phosphorylation of the C-terminus by ATR serves to activate Chk1 by relieving the inhibitory effect of the C-terminus on the N-terminal catalytic domain. However, work carried out in many systems showed that phosphorylation on ATR sites was necessary but not sufficient to increase Chk1 kinase activity. In a recent manuscript we described a single amino acid substitution at an invariant Leucine in the conserve

SUBMITTER: Pereira E 

PROVIDER: S-EPMC4045630 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature