New Functions of Ctf18-RFC in Preserving Genome Stability outside Its Role in Sister Chromatid Cohesion

Expansion of DNA trinucleotide repeats causes at least 15 hereditary neurological diseases, and these repeats also undergo contraction and fragility. Current models to explain this genetic instability invoke erroneous DNA repair or aberrant replication. Here we show that CAG/CTG tracts are stabilized in Saccharomyces cerevisiae by the alternative clamp loader/unloader Ctf18-Dcc1-Ctf8-RFC complex (Ctf18-RFC). Mutants in Ctf18-RFC increased all three forms of triplet repeat instability—expansions, contractions, and fragility—with effect over a wide range of allele lengths from 20–155 repeats. Ctf18-RFC predominated among the three alternative clamp loaders, with mutants in Elg1-RFC or Rad24-RFC having less effect on trinucleotide repeats. Surprisingly, chl1, scc1-73, or scc2-4 mutants defective in sister chromatid cohesion (SCC) did not increase instability, suggesting that Ctf18-RFC protects triplet repeats independently of SCC. Instead, three results suggest novel roles for Ctf18-RFC in facilitating genomic stability. First, genetic instability in mutants of Ctf18-RFC was exacerbated by simultaneous deletion of the fork stabilizer Mrc1, but suppressed by deletion of the repair protein Rad52. Second, single-cell analysis showed that mutants in Ctf18-RFC had a slowed S phase and a striking G2/M accumulation, often with an abnormal multi-budded morphology. Third, ctf18 cells exhibit increased Rad52 foci in S phase, often persisting into G2, indicative of high levels of DNA damage. The presence of a repeat tract greatly magnified the ctf18 phenotypes. Together these results indicate that Ctf18-RFC has additional important functions in preserving genome stability, besides its role in SCC, which we propose include lesion bypass by replication forks and post-replication repair

Fixed point theorems for cyclic self-maps involving weaker Meir-Keelerfunctions in complete metric spaces and applications

We obtain fixed point theorems for cyclic self-maps on complete metric spaces involving Meir-Keeler and weaker Meir-Keeler functions, respectively. In this way, we extend several well-known fixed point theorems and, in particular, improve some very recent results on weaker Meir-Keeler functions. Fixed point results for well-posed property and for limit shadowing property are also deduced. Finally, an application to the study of existence and uniqueness of solutions for a class of nonlinear integral equations is presented.The second author thanks for the support of the Ministry of Economy and Competitiveness of Spain under grant MTM2012-37894-C02-01, and the Universitat Politecnica de Valencia, grant PAID-06-12-SP20120471.Nashine, HK.; Romaguera Bonilla, S. (2013). Fixed point theorems for cyclic self-maps involving weaker Meir-Keelerfunctions in complete metric spaces and applications. Fixed Point Theory and Applications. 2013(224):1-15. https://doi.org/10.1186/1687-1812-2013-224S1152013224Kirk WA, Srinavasan PS, Veeramani P: Fixed points for mapping satisfying cyclical contractive conditions. Fixed Point Theory 2003, 4: 79–89.Banach S: Sur les operations dans les ensembles abstraits et leur application aux equations integerales. Fundam. Math. 1922, 3: 133–181.Boyd DW, Wong SW: On nonlinear contractions. Proc. Am. Math. Soc. 1969, 20: 458–464. 10.1090/S0002-9939-1969-0239559-9Caristi J: Fixed point theorems for mappings satisfying inwardness conditions. Trans. Am. Math. Soc. 1976, 215: 241–251.Di Bari C, Suzuki T, Vetro C: Best proximity points for cyclic Meir-Keeler contractions. Nonlinear Anal. 2008, 69: 3790–3794. 10.1016/j.na.2007.10.014Karapinar E: Fixed point theory for cyclic weaker ϕ -contraction. Appl. Math. Lett. 2011, 24: 822–825. 10.1016/j.aml.2010.12.016Karapinar E, Sadarangani K: Corrigendum to “Fixed point theory for cyclic weaker ϕ -contraction” [Appl. Math. Lett. Vol. 24(6), 822–825.]. Appl. Math. Lett. 2012, 25: 1582–1584. 10.1016/j.aml.2011.11.001Karapinar E, Sadarangani K:Fixed point theory for cyclic ( ϕ − φ ) -contractions. Fixed Point Theory Appl. 2011., 2011: Article ID 69Nahsine HK: Cyclic generalized ψ -weakly contractive mappings and fixed point results with applications to integral equations. Nonlinear Anal. 2012, 75: 6160–6169. 10.1016/j.na.2012.06.021Păcurar M: Fixed point theory for cyclic Berinde operators. Fixed Point Theory 2011, 12: 419–428.Păcurar M, Rus IA: Fixed point theory for cyclic φ -contractions. Nonlinear Anal. 2010, 72: 2683–2693.Piatek B: On cyclic Meir-Keeler contractions in metric spaces. Nonlinear Anal. 2011, 74: 35–40. 10.1016/j.na.2010.08.010Rus IA: Cyclic representations and fixed points. Ann. “Tiberiu Popoviciu” Sem. Funct. Equ. Approx. Convexity 2005, 3: 171–178.Chen CM: Fixed point theory for the cyclic weaker Meir-Keeler function in complete metric spaces. Fixed Point Theory Appl. 2012., 2012: Article ID 17Chen CM: Fixed point theorems for cyclic Meir-Keeler type mappings in complete metric spaces. Fixed Point Theory Appl. 2012., 2012: Article ID 41Meir A, Keeler E: A theorem on contraction mappings. J. Math. Anal. Appl. 1969, 28: 326–329. 10.1016/0022-247X(69)90031-6Matkowski J: Integrable solutions of functional equations. Diss. Math. 1975, 127: 1–68.Karapinar E, Romaguera S, Tas K: Fixed points for cyclic orbital generalized contractions on complete metric spaces. Cent. Eur. J. Math. 2013, 11: 552–560. 10.2478/s11533-012-0145-0De Blasi FS, Myjak J: Sur la porosité des contractions sans point fixed. C. R. Math. Acad. Sci. Paris 1989, 308: 51–54.Lahiri BK, Das P: Well-posedness and porosity of certain classes of operators. Demonstr. Math. 2005, 38: 170–176.Popa V: Well-posedness of fixed point problems in orbitally complete metric spaces. Stud. Cercet. ştiinţ. - Univ. Bacău, Ser. Mat. 2006, 16: 209–214. Supplement. Proceedings of ICMI 45, Bacau, Sept. 18–20 (2006)Popa VV: Well-posedness of fixed point problems in compact metric spaces. Bul. Univ. Petrol-Gaze, Ploiesti, Sec. Mat. Inform. Fiz. 2008, 60: 1–4

Low-spin octahedral cobalt(II) complexes of CoN6 and CoN4P2 chromophores. Synthesis, spectroscopic characterisation and electron-transfer properties

The reaction of 2-(arylazo)pyridines (NC5H4)N=NC6H4R L-1-L-7 (R=H, o-Me/Cl, m-Me/Cl, p-Me/Cl) with cobalt(II) perchlorate hexahydrate in absolute ethanol under anaerobic conditions afforded low-spin [(CoL3)-L-II](2+) complexes, isolated as ClO4- salts. At room temperature the complexes are one-electron paramagnetic in nature, low-spin Co-II, t(2g)(6)e(g)(1), S=1/2 and behave as 1:2 electrolytes in acetonitrile solvent. In acetonitrile solvent they show a ligand-to-metal charge-transfer (LMCT) band near 400 nm, an intraligand transition near 300 nm and ligand-field d-d transitions in the range 860-600 nm. The complexes exhibit quasi-reversible Co-II-Co-III couples near 1 V and six sequential ligand reductions (N=N groups) in the range 0.2 to -1.8 V versus saturated calomel electrode (SCE). At room temperature in the solid state they exhibit isotropic EPR spectra but at 77 K, both in the polycrystalline state and in the dichloromethane solution, display rhombic spectra. Reaction of [(CoL3)-L-II](2+) with 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) resulted in complete ligand-exchanged products with concomitant metal oxidation, low-spin [Co-III(bpy)(3)](3+) and low-spin [Co-III(phen)(3)](3+) respectively. The reaction of PPh3 with the [Ca-II(L-7)(3)](2+) [L-7=2-(p-chlorophenylazo)pyridine] yielded a partial ligand-exchanged product, low-spin [Co-II(L-7)(2)(PPh3)(2)](2+), isolated as its ClO4- salt. The complex is one-electron paramagnet and a 1 :2 electrolyte in acetonitrile solvent. It displays an LMCT band at 401 nm, an intraligand transition at 305 nm and four d-d transitions in the range 870-640 nm. It exhibits irreversible Co-II to Co-III oxidation at 1.33 V (E-pa) and four successive ligand reductions in the range -0.30 to -1.1 V versus SCE. At 77 K the complex displays an axial EPR spectrum

Metal ion-mediated selective activations of C-H and C-Cl bonds. Direct aromatic thiolation reactions via C-S bond cleavage of dithioacids

The reactions of potassium salt of dithiocarbonate, R'OCS2K, 4 (R' = Me, Et, Pr-n, Bu-n, Pr-i, Bu-i, -CH2Ph) with the low-spin ctc-Ru-II(L)(2)Cl-2 1, ctc-Os-II(L)(2)Br-2 2 and mer-[Co-II(L)(3)](ClO4)(2). H2O 3 [L = 2-(arylazo)pyridine, NC5H4-N=N-C6H4(R), R-H, o-Me/Cl, m-Me/Cl, p-Me/Cl; ctc: cis-trans-cis with respect to halides, pyridine and azo nitrogens respectively) in boiling dimethylformamide solvent resulted in low-spin diamagnetic Ru-II(L')(2), 5, Os-II(L')(2) 6 and [Co-III(L')(2)]ClO4 7 respectively (L' = o-S-C6H3(R)N=NC5H4N). In the complexes 5, 6 and 7 ortho carbon-hydrogen bond of the pendant phenyl ring of the ligands (L') has been selectively and directly thiolated via the carbon-sulphur bond cleavage of 4. The newly formed tridenate thiolated ligands (L') are bound to the me;al ion in a meridional fashion. In the case of cobalt complex (7), during the activation process the bivalent cobalt ion in the starting complex 3 has been oxidised to the trivalent Co-III state. The reactions are highly sensitive to the nature and the location of the substituents present in the active phenyl ring. The presence of electron donating Me group at the ortho and para positions of the pendant phenyl ring with respect to the activation points can only facilitate the thiolation process. The complexes (1c, 2c and 3c) having chloride group at the ortho position of the active phenyl ring underwent the thiolation reaction selectively via the carbon-chloride bond activation process. The rate of carbon-chloride activation process has been found to be much faster compared to the C-H bond activation. The reactions are sensitive to the nature of the solvent used, taking place only in those having high boiling and polar solvents. The rate of the reactions is also dependent on the nature of the R' group present in 4, following the order: Me similar to Et > Pr-n > Bu-n > Pr-i > Bu-i >> -CH2Ph. The molecular geometry of the complexes in solution has been established by H-1 and C-13 NMR spectroscopy. The thiolated complexes (5, 6, 7) exhibit metal to ligand charge-transfer transitions in the visible region and intraligand pi-pi* and n-pi* transitions in the UV region. In acetonitrile solution the complexes display reversible M(III)reversible arrow M-II reductions at 0.43 V for Ru (5a), 0.36 V for Os (6a) and -0.13 V for Co (7a) vs saturated calomel electrode (SCE)

Ruthenium-, osmium- and cobalt-ion mediated selective activation of a C-Cl bond. Direct and spontaneous aromatic thiolation reaction via C-S bond cleavage

The reactions of KSC(S)OEt and NaSC(S)NEt2 with the complexes [RuL2Cl2] 1a, [OsL2Br2] 1b and [CoL3[ClO4](2).H2O 1c [L = 2-(o-chlorophenylazo)pyridine, 2-(o-ClC6H4N=N)C5H4N] in boiling dimethylformamide solvent resulted in [(RuL)-L-II'(2)] 3a, [(OsL)-L-II'(2)] 3b and [(CoL)-L-III'(2)][ClO4] 3c respectively [L' = 2-(o-SC6H4N=N)C5H4N]. In complexes 3 the o-carbon-chlorine bond of the pendant phenyl ring of the parent ligand L has been selectively and directly thiolated via carbon-sulfur bond cleavage of the dithiocarbonate and dithiocarbamate molecules, Two such newly formed tridentate thiolated ligands (L') are bound to the metal ions in a meridional fashion. The reactions are spontaneous in the case of dithiocarbonate as thiolating agent, but relatively slow and incomplete for dithiocarbamate. During the thiolation reaction the metal ion in the cobalt complex is oxidised from the starting Co-II in 1c to Co-III in the final product 3c. The reactions are highly sensitive to the nature of the solvent used, taking place only in those having high boiling points and polarities. The meridional configuration (cis-trans-cis with respect to sulfur, azo and pyridine nitrogens respectively) of 3 has been established by H-1 and C-13 NMR spectroscopy. The complexes exhibit two MLCT transitions in the visible region and intraligand (pi-pi*, n-pi*) transitions in the UV region. In acetonitrile solution they display reversible M-III-M-II reduction potentials at 0.43 V for Ru (3a), 0.36 V for Os (3b) and -0.14 V for Co (3c) versus the saturated calomel electrode

Cobalt-mediated direct and selective aromatic thiolation in the complex [Co-III(o-SC6H4N=NC5H4N)(2)]ClO4. Synthesis, spectroscopic characterisation and electron-transfer properties

The reaction of K[SC(S)OR] (R = Me, Et, Pr-n, Pr-i, Bu-n, Bu-i or CH2Ph) with the complex [(CoL3)-L-II][ClO4](2) . H2O 1 [L = phenyl(2-pyridyl)diazene, C6H5N=NC5H4N] in boiling dimethylformamide resulted in [(CoL)-L-III'(2)]ClO4 2 (L' = o-SC6H4N=NC5H4N). In complex 2 the o-carbon-hydrogen bond of the pendant phenyl ring of both the parent ligands L has been selectively and directly thiolated via carbon-sulfur bond cleavage of the dithiocarbonate. During the thiolation the metal ion is oxidised from the starting Co-II in 1 to Co-III in the final product 2. The reaction is highly sensitive to the nature of the solvent used, taking place only in those having high boiling points and relative permittivities. Its rate is dependent,n the: nature of the R group present in the thiolating agent, following the order Me approximate to Et > Pr-n > Bu-n > Pr-i > Bu-i much greater than benzyl. A meridional configuration (cis-trans-cis with respect to the sulfur, azo and pyridine nitrogens respectively) has been established by H-1 and C-13 NMR spectroscopy. The complex exhibits reversible Co-III reversible arrow Co-II reduction at -0.135 V and four ligand-based azo (N=N) reductions at -0.51 (one electron) and at -1.175 V (simultaneous three-electron reduction) respectively versus saturated calomel electrode. The oxidation of the co-ordinated thiol group occurs at 0.90 V