Caspase-mediated cleavage of claspin

Claspin is cleaved by caspase-7 during the initiation of apoptosis following DNA damage (Clarke et al., 2005). Claspin is cleaved at a single aspartate residue into a large N-terminal fragment and a smaller C-terminal fragment that contain different functional domains. Only the large N-terminal fragment retains Chk1 binding activity. The smaller C-terminal fragment associates with DNA and inhibits the DNA-dependent phosphorylation of Chk1 associated with its activation indicating that cleavage of Claspin by caspase-7 inactivates the Chk1 signaling pathway (Clarke et al., 2005).

Claspin 在DNA损伤引发的细胞凋亡启动阶段被caspase-7酶解（Clarke 等人，2005年）。Claspin 在单个天冬氨酸残基处被切割，形成一个大型的N端片段和一个小型的C端片段，两者含有不同的功能结构域。仅有大型N端片段保持与Chk1的结合活性。小型C端片段与DNA结合并抑制与Chk1激活相关的DNA依赖性磷酸化，表明Claspin被caspase-7切割将使Chk1信号通路失活（Clarke 等人，2005年）。