RIF1
Description
The RIF1 (replication timing regulatory factor 1) is a protein-coding gene located on chromosome 2.
RIF1, or Rap1-interacting factor 1 homolog, is a protein encoded by the RIF1 gene in humans. In yeast, RIF1 and RIF2 protect chromosome ends (telomeres). In higher eukaryotes, RIF1 participates in DNA damage response, chromatin architecture organization, and replication timing regulation. It has been demonstrated to bind RNA within the nucleus.
RIF1 is a key regulator of TP53BP1, playing a crucial role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage. It promotes non-homologous end joining (NHEJ)-mediated repair of DSBs. Upon DNA damage, RIF1 interacts with ATM-phosphorylated TP53BP1, leading to the dissociation of NUDT16L1/TIRR from TP53BP1. This unmasks the tandem Tudor-like domain of TP53BP1, allowing its recruitment to DNA DSBs. Once at the DSBs, RIF1 and TP53BP1 further promote NHEJ-mediated repair. Simultaneously, they counteract BRCA1 function by blocking DSBs resection via homologous recombination (HR) during the G1 phase. RIF1 is also essential for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process involving DNA DSBs. It promotes NHEJ of dysfunctional telomeres.
RIF1 is also known as -.
