RIF1

Found in the nucleus of germinal-vesicle (GV) stage oocytes prior to fertilization. Accumulates in the male and female pronucleus after fertilization. Expressed in the nuclei of all blastomeres from the two cell stage to the compacted morula stage, although absent from the polar body and inner cell mass (ICM). Found in the nuclei of polar and mural trophectoderm cells from 3.5 dpc, and at high levels in the epiblast from 5.5 dpc to 7.5 dpc. Expressed by primitive germ cells (PGCs) in both male and female from 9.5 dpc to 13.5 dpc, at which point expression declines. A low level is observed in Sertoli cells of the testis at 17.5 dpc.

Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:23306437, PubMed:23306439, PubMed:23333305). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23306437, PubMed:23306439, PubMed:23333305). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (By similarity). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23306437, PubMed:23333305). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23306437, PubMed:23333305). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23306439, PubMed:23333305, PubMed:23333306). Promotes NHEJ of dysfunctional telomeres (PubMed:23333305).

Belongs to the RIF1 family.

Expressed in Sertoli cells, prospermatagonia, early primary spermatocytes, and in oocytes at all stages of their growth. Expressed in embryonic stem (ES) and embryonic germ (EG) cells: expression is lost upon differentiation.

• Nucleus
• Chromosome
• Chromosome
• Telomere
• Cytoplasm
• Cytoskeleton
• Spindle
• Exhibits ATM- and TP53BP1-dependent localization to uncapped or aberrant telomeres and to DNA double strand breaks (DSBs). Following interaction with TP53BP1, recruited to sites of DNA damage, such as DSBs (PubMed:23306437, PubMed:23306439, PubMed:23333305). Localizes to microtubules of the midzone of the mitotic spindle during anaphase, and to condensed chromosomes in telophase (By similarity). While the majority of the protein appears nuclear and distinct from normal telomere structures, a small fraction may bind to telomeres in embryonic stem cells (PubMed:15042697).

Telomere-associated protein RIF1, Rap1-interacting factor 1 homolog, mRif1, Rif1

• entrezGene:51869
• swissprot:Q6PR54

Proteins

Oncology

266228Da