UniProt functional annotation for O60921



	UniProt functional annotation for O60921

UniProt code: O60921.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:21659603}.

Subunit: Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1. The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2. The 9-1-1 complex associates with the RAD17-RFC complex. HUS1 interacts with POLB, HDAC1, FEN1, PCNA, RAD1, RAD9A and RAD9B. HUS1 does not interact with RAD17. Interacts with DNAJC7. {ECO:0000269|PubMed:10359610, ECO:0000269|PubMed:10777662, ECO:0000269|PubMed:10846170, ECO:0000269|PubMed:10884395, ECO:0000269|PubMed:11077446, ECO:0000269|PubMed:11573955, ECO:0000269|PubMed:14500360, ECO:0000269|PubMed:14611806, ECO:0000269|PubMed:15314187, ECO:0000269|PubMed:15556996, ECO:0000269|PubMed:15871698, ECO:0000269|PubMed:15897895, ECO:0000269|PubMed:16216273}.

Subcellular location: Nucleus {ECO:0000269|PubMed:10846170, ECO:0000269|PubMed:11077446}. Cytoplasm, cytosol {ECO:0000269|PubMed:11077446}. Note=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. {ECO:0000269|PubMed:11077446}.

Tissue specificity: Ubiquitous. {ECO:0000269|PubMed:10777662}.

Similarity: Belongs to the HUS1 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:21659603}.


Subunit:		Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1. The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2. The 9-1-1 complex associates with the RAD17-RFC complex. HUS1 interacts with POLB, HDAC1, FEN1, PCNA, RAD1, RAD9A and RAD9B. HUS1 does not interact with RAD17. Interacts with DNAJC7. {ECO:0000269\|PubMed:10359610, ECO:0000269\|PubMed:10777662, ECO:0000269\|PubMed:10846170, ECO:0000269\|PubMed:10884395, ECO:0000269\|PubMed:11077446, ECO:0000269\|PubMed:11573955, ECO:0000269\|PubMed:14500360, ECO:0000269\|PubMed:14611806, ECO:0000269\|PubMed:15314187, ECO:0000269\|PubMed:15556996, ECO:0000269\|PubMed:15871698, ECO:0000269\|PubMed:15897895, ECO:0000269\|PubMed:16216273}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:10846170, ECO:0000269\|PubMed:11077446}. Cytoplasm, cytosol {ECO:0000269\|PubMed:11077446}. Note=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. {ECO:0000269\|PubMed:11077446}.
Tissue specificity:		Ubiquitous. {ECO:0000269\|PubMed:10777662}.
Similarity:		Belongs to the HUS1 family. {ECO:0000305}.