Hus1 is a component of the 9-1-1 cell-cycle checkpoint response complex (which consists of Rad9, Hus1, Rad1), a key complex in the coordination of DNA damage sensing, cell cycle progression and DNA repair pathways. In humans, the 9-1-1 complex is recruited to DNA lesions upon damage by the RAD17-replication factor C (RFC) clamp loader complex. It activates checkpoint response and acts as a sliding clamp platform on DNA for several proteins involved in DNA repair. The 9-1-1 complex is necessary for the recruitment of C12orf32/RHINO to sites of double-stranded breaks (DSB) occurring during the S phase [].
This entry consists of the human Hus1 protein and budding yeast Mec3. They are components of the checkpoint clamp complex involved in the surveillance mechanism that allows the DNA repair pathways to act to restore the integrity of the DNA prior to DNA synthesis or separation of the replicated chromosomes [, ]. Hus1, Rad1, and Rad9 (which share homology with Mec1, Rad17, Ddc1 in budding yeast) are three evolutionarily conserved proteins required for checkpoint control. These proteins are known to form a stable complex. Structurally, the Ddc1-Mec3-Rad17 complex is similar to the PCNA complex, which forms trimeric ring-shaped clamps. Ddc1-Mec3-Rad17 plays a role in checkpoint activation that permits DNA-repair pathways to prevent cell cycle progression in response to DNA damage and replication stress [, ].
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.
