Claspin

Definition:

Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation. Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins. Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS. Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components.

References:

[1]. Yasemin Baris, et al. Fast and efficient DNA replication with purified human proteins. Nature. 2022 Jun;606(7912):204-210. [Content Brief]

[2]. Chi-Chun Yang, et al. Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells. Nat Commun. 2016 Jul 12;7:12135. [Content Brief]

[3]. Claudia Christiano Silva Chini, et al. Human claspin is required for replication checkpoint control. J Biol Chem. 2003 Aug 8;278(32):30057-62. [Content Brief]

[4]. Catriona A L Clarke, et al. DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system. Biochem J. 2005 Jun 1;388(Pt 2):705-12. [Content Brief]

[5]. Catriona A L Clarke, et al. Cleavage of claspin by caspase-7 during apoptosis inhibits the Chk1 pathway. J Biol Chem. 2005 Oct 21;280(42):35337-45. [Content Brief]

[6]. Funda Sar, et al. Human claspin is a ring-shaped DNA-binding protein with high affinity to branched DNA structures. J Biol Chem. 2004 Sep 17;279(38):39289-95. [Content Brief]

[7]. Morgan L Jones, et al. Structure of a human replisome shows the organisation and interactions of a DNA replication machine. EMBO J. 2021 Dec 1;40(23):e108819. [Content Brief]

[8]. Claus Storgaard Sørensen, et al. ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage. Cell Cycle. 2004 Jul;3(7):941-5. [Content Brief]

[9]. Shiaw-Yih Lin, et al. Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6484-9. [Content Brief]

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