5nvr
From Proteopedia
Crystal structure of the Rif1 N-terminal domain (RIF1-NTD) from Saccharomyces cerevisiae
Structural highlights
FunctionRIF1_YEAST Negatively regulates telomere length by preventing telomere elongation or promoting degradation of the telomere ends. Recruited to telomeres by interaction with the C-terminus of RAP1, which binds directly to telomeric repeat DNA. This may create a negative feedback loop in which the addition of new telomere repeats creates binding sites for inhibitors of telomere length extension. May also influence the balance of transcriptional silencing at telomeres and the silent mating type locus HMR, which is mediated by SIR (Silent Information Regulator) proteins including SIR3 and SIR4. RIF1 competes with SIR proteins for binding to the C-terminus of RAP1. In the absence of RIF1, a limiting cellular pool of SIR proteins may preferentially associate with RAP1 at sub-telomeric loci, causing enhanced telomeric silencing and attenuated silencing of the HMR locus.[1] [2] [3] [4] [5] Publication Abstract from PubMedIn yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved approximately 125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an alpha-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer. Engagement of the Rif1-NTD with telomeres proved essential for checkpoint control and telomere length regulation. Unexpectedly, Rif1-NTD also promoted NHEJ at DNA breaks in yeast, revealing a conserved role of Rif1 in DNA repair. We propose that tight associations between the Rif1-NTD and DNA gate access of processing factors to DNA ends, enabling Rif1 to mediate diverse telomere maintenance and DNA repair functions. Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends.,Mattarocci S, Reinert JK, Bunker RD, Fontana GA, Shi T, Klein D, Cavadini S, Faty M, Shyian M, Hafner L, Shore D, Thoma NH, Rass U Nat Struct Mol Biol. 2017 Jul;24(7):588-595. doi: 10.1038/nsmb.3420. Epub 2017, Jun 12. PMID:28604726[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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