Protein: Breast cancer type 1 susceptibility protein homolog (EC 2.3.2.27) (RING-type E3 ubiquitin transferase BRCA1) (B6VQ60)
Organism: Caenorhabditis elegans
Function: E3 ubiquitin-protein ligase that specifically mediates the formation of polyubiquitin chains and plays a central role in DNA repair. Plays a role in triggering cellular responses at damage sites in response to DNA damage that may be induced by UV and ionizing radiation for example. Functions in double-strand break repair, and is required for homologous recombination between sister chromatids in meiotic and mitotic cells. In particular, protects against chromosome non-disjunction and nuclear fragmentation during meiotic double-strand break repair to ensure sister chromatid recombination and aid chromosome stability. Required for normal cell cycle progression. Along with brap-2 modulates the expression of cell cycle arrest protein cki-1 in response to increased levels of reactive oxygen species. Constituent of the CeBCD complex that possesses E3 ubiquitin-protein ligase activity. When bound to chromatin, the brc-1-brd-1 heterodimer within the CeBCD complex is inactive during normal conditions, but in response to DNA damage, the brc-1-brd-1 heterodimer associates with other proteins such as the recombinase rad-51 or the E2-ubiquitin-conjugating enzyme let-70, which activate the CeBCD complex as an E3-ubiquitin ligase. Moreover, association between the brc-1-brd-1 heterodimer and rad-51 and let-70, probably requires DNA checkpoint proteins such as atl-1 and mre-11 in order to induce ubiquitination at DNA damage sites. To this end, the brc-1-brd-1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability.
Subcellular location: Nucleus {ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:30383754}. Chromosome {ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:30383754}. Cytoplasm {ECO:0000269|PubMed:16628214}. Note=Mainly localizes to the nucleus and a small proportion is chromatin bound (PubMed:30383754). Co-localizes with brd-1 in germline nuclei at meiotic prophase I (PubMed:30383754). At the transition between mid- and late- pachytene, localization together with brd-1 is less diffuse and becomes a linear pattern along the chromosomes (PubMed:30383754). In late pachytene nuclei, co-localizes with brd-1 and syp-1 at crossover sites and the short arm of the bivalent (PubMed:30383754). Co-localizes with the pro-crossover factors cosa-1, zhp-3 and msh-5 at crossover sites in mid-late pachytene nuclei (PubMed:30383754). Co-localizes with plk-2 in pachytene nuclei (PubMed:30383754). Localizes to DNA damage sites on chromatin following DNA damage. {ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:30383754}.
Interaction partners:
- BRCA1-associated RING domain protein 1
- DNA repair protein RAD51 homolog
- FANCD2
- DNA endonuclease activator Ctp1 C-terminal domain-containing protein
- BRCT domain-containing protein
- Helicase ATP-binding domain-containing protein
- Double-strand break repair protein mre-11
- Uncharacterized protein K02D10.4
- ATP-dependent DNA helicase II subunit 2
- Serine/threonine-protein kinase ATM
Sequence:
MADVALRITETVARLQKELKCGICCSTYKDPILSTCFHIFCRSCINACFERKRKVQCPICRSVLDKRSCRDTYQITMAVQNYLKLSEAFKKDIENMNTFKSLPPEKMFMESQMPLDITIIPENDGKRCAPDFAIPFLPVRRKRPSRPQPPSAFAEEPAEPVEPPEPATKQPVELQSRVFPLEKLKKDVETSTETYKISREELKNVDIEEYINTLRENSTEIDEIDALFQLMPTMRQFLRNNINQLMEKFHVAPPKKSEKPANRRVSFASSQDLENIKIMTASESLETPPEPIQKLAQKPEVFKSTQNLIDLNLNTAVKKPVVVASDDDEVVEDSEGELQIDEDDLANVTCATSSTTLDADRTPKAIQDDEDRIDDELSQVPKTIVCSRIHNDADEVVGLELLSDFYHKFLSNACRFAEDVNEHTTHLVMMNSEGRSISQKSTAYLYAIARKCVIVGRQWLVDCITTGLLLSEADYTITSCSSTIPVKIPPSIGSEMGWLRSRNDEHGKLFAGRRFMILRKFTMNPYFDYKQLIELVQQCGGEILSCYENLSPEKLYIIFSKHSKAIEESKNIENLYKCDVVTMEWVLDSISEYLILPTQPYKAVDSIGCLQD