RIF1: a novel regulatory factor for DNA replication and DNA damage response signaling.
DNA double strand breaks (DSBs) are highly toxic to the cells and accumulation of DSBs results in several detrimental effects in various cellular processes which can lead to neurological, immunological and developmental disorders. Failure of the repair of DSBs spurs mutagenesis and is a driver of tumorigenesis, thus underscoring the importance of the accurate repair of DSBs. Two major canonical DSB repair pathways are the non-homologous end joining (NHEJ) and homologous recombination (HR) pathways. 53BP1 and BRCA1 are the key mediator proteins which coordinate with other components of the DNA repair machinery in the NHEJ and HR pathways respectively, and their exclusive recruitment to DNA breaks/ends potentially decides the choice of repair by either NHEJ or HR. Recently, Rap1 interacting factor 1 has been identified as an important component of the DNA repair pathway which acts downstream of the ATM/53BP1 to inhibit the 5'-3' end resection of broken DNA ends, in-turn facilitating NHEJ repair and inhibiting homology directed repair. Rif1 is conserved from yeast to humans but its function has evolved from telomere length regulation in yeast to the maintenance of genome integrity in mammalian cells. Recently its role in the maintenance of genomic integrity has been expanded to include the regulation of chromatin structure, replication timing and intra-S phase checkpoint. We present a summary of these important findings highlighting the various aspects of Rif1 functions and discuss the key implications for genomic integrity.
IFOM-p53Lab Joint Research Laboratory, 8A Biomedical Grove, #06-38, Immunos, A*STAR, S138648 Singapore, Singapore; IFOM, The FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy.
Ramesh
R
Kumar
IFOM-p53Lab Joint Research Laboratory, 8A Biomedical Grove, #06-38, Immunos, A*STAR, S138648 Singapore, Singapore; IFOM, The FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, S117597 Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, 50 Nanyang Avenue, S639798 Singapore, Singapore. Electronic address: cfcheok@jrl.a-star.edu.sg.
Chit Fang
CF
Cheok
D000818:Animals; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004261:DNA Replication; D042822:Genomic Instability; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D015398:Signal Transduction; D016615:Telomere / Q000235:genetics; D034501:Telomere-Binding Proteins / Q000502:physiology*; D000071857:Tumor Suppressor p53-Binding Protein 1
D047908:Intracellular Signaling Peptides and Proteins; C492743:Rif1 protein, human; C498301:TP53BP1 protein, human; D034501:Telomere-Binding Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1
DNA repair; Genomic integrity; Nonhomologous end joining; Replication; Telomere