HUS1

HUS1

A gene on chromosome 7p13-p12 that belongs to an evolutionarily conserved, genotoxin-activated checkpoint complex, which triggers cell-cycle arrest in response to DNA damage. HUS1 forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1, which then interacts with another protein complex—checkpoint protein RAD17 and 4 small subunits of the replication factor C—loading the complex onto the chromatin. The DNA damage induced-chromatin binding depends on activation of checkpoint kinase ATM, and may be an early checkpoint-signalling event.
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Araya , Loss of Hus1 sensitizes cells to etoposide-induced apoptosis by regulating BH3-only proteins,Oncogene,27, 7248 (2008).
Pei et al., "Cadmium-induced germline apoptosis in Caenorhabditis elegans: the roles of HUS1, p53, and MAPK signaling pathways," Toxicological Sciences, vol.
Protein function S.cerevisiae S.pombe Xenopus Mammals Sensors Rad24 Rad17 Rad17 Rad17 RFC-like Ddc1 Rad9 Rad9 Rad9 PCNA-like Mec3 Hus1 Hus1 Hus1 Rad17 Rad1 Rad1 Rad1 P13-Kinases (PIKK) Tel1 Tel1 ATM ATM Med Rad3 ATR ATR PIKK binding partner Ddc2 Rad26 ???
The candidate DNA damage sensors Rad9, Hus1, and Rad1 form a ring structure (the "9-1-1" complex) that can encircle the DNA similar to PCNA (Melo and Toczyski, 2002).
When they inactivated the Hus1 gene in healthy mammary gland tissues, it caused genome damage and cell death.
They have discovered that inactivation of a DNA repair gene called Hus1 efficiently kills cells lacking p53 - a gene mutated in the majority of human cancers.
And when they studied the effects of Hus1 inactivation in p53-deficient cells, which are highly resistant to cell death, they discovered that the ability of Hus1 inactivation to kill cells was even greater.
"We were able to exploit one such dependency of p53-deficient cells and could efficiently kill these cells by inhibiting Hus1," he added.