Treslin, a TopBP1-interacting protein, is necessary for DNA replication in vertebrates []. Prior to the initiation of DNA replication, treslin associates with TopBP1 in a Cdk2-dependent manner []. The proteins then collaborate in the Cdk2-mediated loading of Cdc45 onto replication origins [].Treslin is also an important checkpoint regulator, and is required to prevent mitotic entry after treatment with ionizing radiation [].
TopBP1, also termed DNA topoisomerase II-beta-binding protein 1, functions in DNA replication and damage response. It binds double-stranded DNA breaks and nicks as well as single-stranded DNA []. It has been shown to activate the ATR-ATRIP complex []. TopBP1 contains six copies of BRCT domain. The entry corresponds to the first BRCT domain, which is a protein-protein binding module [].
This entry represents Rad9, Rad1, Hus1-interacting nuclear orphan protein 1 (RHINO or RHNO1), which plays a role in DNA damage response (DDR) signalling upon genotoxic stresses such as ionizing radiation (IR) during the S phase []. RHNO1 is recruited to sites of DNA damage through interaction with the Rad9-Rad1-Hus1 (9-1-1) complex and ATR activator TopBP1. It plays a role in ATR-mediated activation of Chk1 driven by TopBP1 and 9-1-1 []. It is involved in mammary carcinogenesis [].
This entry includes DNA damage checkpoint proteins Rad9. Rad9 is required for transient cell-cycle arrests and transcriptional induction of DNA repair in response to DNA damage []. It is worth noting that this entry including the mamalian Rad9, which is homologous to the fission yeast Rad9 and the budding yeast Ddc1. Members of this family do not share the sequence homology with the budding yeast Rad9.Rad9 forms a complex with Hus1 and Rad1, called 9-1-1 complex. In human, 9-1-1 binds to TopBP1 and activates the ATR-Chk1 checkpoint pathway []. Rad9 also shows 3'-5' exonuclease activity []. Besides its function in the 9-1-1 complex, Rad9 can act as a transcriptional factor, participate in immunoglobulin classswitch recombination []. Aberrant Rad9 expression has been associated with prostate, breast, lung, skin, thyroid, and gastric cancers [].
This entry represents the DNA damage checkpoint protein Rad9 and its homologue in budding yeast, Ddc1. Rad9 forms a complex with Hus1 and Rad1 (called 9-1-1 complex). Ddc1 forms a similar complex with Mec1 and Rad17. Structurally, the 9-1-1 / Ddc1-Mec3-Rad17 complex is similar to the PCNA complex, which forms trimeric ring-shaped clamps. The 9-1-1 / Ddc1-Mec3-Rad17 complex plays a role in checkpoint activation that permits DNA-repair pathways to prevent cell cycle progression in response to DNA damage and replication stress [, ].In humans, 9-1-1 binds to TopBP1 and activates the ATR-Chk1 checkpoint pathway []. Besides its function in the 9-1-1 complex, Rad9 can also act as a transcriptional factor and participate in immunoglobulin class switch recombination []. It also shows 3'-5' exonuclease activity []. Aberrant Rad9 expression has been associated with prostate, breast, lung, skin, thyroid, and gastric cancers [].In budding yeast, Ddc1 can activate Mec1 (the principal checkpoint protein kinase, human ATR homologue) in G1 phase. In G2 phase, Ddc1 can either activate Mec1 directly or recruit Dpb11 (the orthologue of human TopBP1) and subsequently activate Mec1 []. Ddc1 does not have DNA exonuclease function [].It is worth noting that the Rad9 proteins referred to in this entry are the mammalian and fission yeast homologues of budding yeast Ddc1. Members of this family do not share the sequence homology another DNA damage-dependent checkpoint protein from budding yeast, confusingly also called Rad9.
