HUS1

The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. This protein forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1. In response to DNA damage, the trimeric complex interacts with another protein complex consisting of checkpoint protein RAD17 and four small subunits of the replication factor C (RFC), which loads the combined complex onto the chromatin. The DNA damage induced chromatin binding has been shown to depend on the activation of the checkpoint kinase ATM, and is thought to be an early checkpoint signaling event. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]

Full Name

HUS1 Checkpoint Clamp Component

Function

Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase.

Biological Process

Cellular response to DNA damage stimulus Source: ProtInc
Cellular response to ionizing radiation Source: UniProtKB
DNA damage checkpoint signaling Source: UniProtKB
DNA repair Source: ProtInc
Double-strand break repair via homologous recombination Source: GO_Central
Embryo development ending in birth or egg hatching Source: Ensembl
Meiotic DNA integrity checkpoint signaling Source: GO_Central
Mitotic DNA replication checkpoint signaling Source: GO_Central
Mitotic intra-S DNA damage checkpoint signaling Source: GO_Central
Nucleotide-excision repair Source: GO_Central
Protein phosphorylation Source: Ensembl
Regulation of protein phosphorylation Source: Ensembl
Response to UV Source: Ensembl
Telomere maintenance Source: GO_Central

Cellular Location

Cytosol; Nucleus. In discrete nuclear foci upon DNA damage. According to PubMed:11077446, localized also in the cytoplasm. DNA damage induces its nuclear translocation. Shuttles between the nucleus and the cytoplasm.