RIF1

This gene encodes a protein that shares homology with the yeast teleomere binding protein, Rap1 interacting factor 1. This protein localizes to aberrant telomeres may be involved in DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

Full Name

Replication Timing Regulatory Factor 1

Function

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:15342490, PubMed:28241136).
In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136).
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 (PubMed:28241136).
Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306).
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:23333306).
Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity).
Promotes NHEJ of dysfunctional telomeres (By similarity).

Biological Process

Biological Process cell cycleIEA:UniProtKB-KW
Biological Process cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process cellular response to leukemia inhibitory factorIEA:Ensembl
Biological Process DNA repairIEA:UniProtKB-KW
Biological Process negative regulation of double-strand break repair via homologous recombinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of gene expression, epigeneticISS:BHF-UCL
Biological Process negative regulation of transcription by RNA polymerase IIISS:BHF-UCL
Biological Process positive regulation of double-strand break repair via nonhomologous end joiningManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of histone H3-K9 methylationISS:BHF-UCL
Biological Process positive regulation of isotype switchingISS:UniProtKB
Biological Process somatic stem cell population maintenanceIEA:Ensembl
Biological Process subtelomeric heterochromatin assemblyISS:BHF-UCL
Biological Process telomere maintenanceISS:BHF-UCL
Biological Process telomere maintenance in response to DNA damageManual Assertion Based On ExperimentIDA:BHF-UCL

Cellular Location

Nucleus
Chromosome
Chromosome, telomere
Cytoplasm, cytoskeleton, spindle
Following interaction with TP53BP1, recruited to sites of DNA damage, such as DSBs (By similarity).
Exhibits ATM- and TP53BP1-dependent localization to uncapped or aberrant telomeres and to DNA double strand breaks (DSBs) (PubMed:15342490).
Does not associate with normal telomere structures (PubMed:15342490, PubMed:15583028).
Localizes to microtubules of the midzone of the mitotic spindle during anaphase, and to condensed chromosomes in telophase (PubMed:15583028).