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Vega, H. et al. Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion. Nature Genet. 37, 468-470

Johns Hopkins University, Baltimore, Maryland, United States
Nature Genetics (Impact Factor: 29.65). 06/2005; 37(5):468-70. DOI: 10.1038/ng1548
Source: PubMed

ABSTRACT Roberts syndrome is an autosomal recessive disorder characterized by craniofacial anomalies, tetraphocomelia and loss of cohesion at heterochromatic regions of centromeres and the Y chromosome. We identified mutations in a new human gene, ESCO2, associated with Roberts syndrome in 15 kindreds. The ESCO2 protein product is a member of a conserved protein family that is required for the establishment of sister chromatid cohesion during S phase and has putative acetyltransferase activity.

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    • "(/BRCA2) p.Ala938Profs*21 p.Lys3326* EUFA178-L M FANCB a Deletion promoter exon 1 – [34] No protein EUFA1386-L M FANCB a c.829dup – [34] p.Cys277Leufs*31 EUFA158-L F FANCC c.67del (also known as 322delG) c.67del (also known as 322delG) [35] p.Asp23Ilefs*23 p.Asp23Ilefs*23 EUFA1289-L M FANCD2 c.206-2A > T c.1414- 71 1545 + 256del459 [36] p.Ala69Aspfs*7 p.Glu472 Lys515del EUFA816-L M FANCI c.3853C > T c.3350-88A > G [37] p.Arg1285* p.Glu1117fs EUFA868-L F FANCL c.837-15 837-9delins177 c.837-15 837-9delins177 [38] p.? p.? EUFA867-L F FANCM c.2171C > A c.4222 + 1978 4300del [39] p.Ser724* p.? FANCA c.2557C > T c.709 + 5G > A [29] p.Arg853* p.? HSC62 M FANCD1 c.8488-1G > A c.8488-1G > A [20] (/BRCA2) p.Trp2830 Lys2833del p.Trp2830 Lys2833del EUFA208-L F FANCD1 c.7878G > C c.756 757del Current study (/BRCA2) p.Trp2626Cys p.Asp252Glufs*2 EUFA423-L F FANCD1 c.7463 7464insAT c.9672dup [20] (/BRCA2) p.Asp2489* p.Tyr3225Ilefs*30 EUFA579-L F FANCD1 c.7007G > A 5609 5610delinsAG [20] (/BRCA2) p.? p.Phe1870* EUFA932-L M FANCD1 c.2957dup c.7684T > C Current study (/BRCA2) p.Asn986Lysfs*2 p.Phe2562Leu EUFA943-L M FANCD1 c.480 489del c.480 489del Current study (/BRCA2) p.Gly162Phefs*7 p.Gly162Phefs*7 EUFA1389-L F FANCD1 c.1597del Deletion exon 15–16 Current study (BRCA2) p.Thr533Leufs*25 p.? EUFA696-L F FANCJ c.2392C > T c.2492 + 2dup [40] (/BRIP1) p.Arg798* p.? EUFA1341-L F FANCN c.1653T > A Deletion exon 1–10 [21] (/PALB2) p.Tyr551* p.? EUFA1354-L M FANCP c.286del c.286del [24] (/SLX4) p.Thr96Leufs*30 p.Thr96Leufs*30 FA104 F FANCQ c.1484 1488del c.2065C > A [27] (/XPF) p.Thr495Asnfs*6 p.Arg689Ser VU1177-L F ESCO2 c.1111dup c.1111dup [41] p.Thr371Asnfs*32 p.Thr371Asnfs*32 VU1199-L M ESCO2 c.879 880del c.879 880del [41] p.Arg293Serfs*7 p.Arg293Serfs*7 VU1202-L M DDX11 c.2689 2691del c.2271 + 2T > C [30] p. Lys897del p.? CdLS11165 M NIPBL b c.3813 3815del – [42] p.Lys1271del CdLS11167 F NIPBL b c.3940dup – [42] p.Thr1314Asnfs*9 EUFA1341F SV40 F FANCN c.1653T > A Deletion exon 1–10 [21] (/PALB2) p.Tyr551* p.? VU1199F SV40 M ESCO2 c.879 880del c.879 880del [41] p.Arg293Serfs*7 p.Arg293Serfs*7 VU-SCC-1131 F FANCC c.67del (also known as 322delG) c.67del (also known as 322delG) [43] p.Asp23Ilefs*23 p.Asp23Ilefs*23 VU-SCC-1365 M FANCA c.3788-3790del c.3788-3790del [43] p. Phe1263del p.Phe1263del VU-SCC-1604 F FANCL c.483 487del c.906C > G Current study p.Glu161Aspfs*31 p.Ile302Met a X-linked inheritance. b Autosomal dominant "
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    • "Arabidopsis CTF7 is required for microsporogenesis 3 situation previously observed in mutations for human ESCO2 (Vega et al., 2005). "
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    ABSTRACT: The proper transmission of DNA in dividing cells is crucial for the survival of eukaryotic organisms. During cell division, faithful segregation of replicated chromosomes requires their tight attachment, known as sister chromatid cohesion, until anaphase. Sister chromatid cohesion is established during S-phase in a process requiring an acetyltransferase that in yeast is known as Establishment of cohesion 1 (Eco1). Inactivation of Eco1 typically disrupts chromosome segregation and homologous recombination-dependent DNA repair in dividing cells, ultimately resulting in lethality. We report here the isolation and detailed characterization of two homozygous T-DNA insertion mutants for the Arabidopsis thaliana Eco1 homolog, CHROMOSOME TRANSMISSION FIDELITY 7/ESTABLISHMENT OF COHESION 1 (CTF7/ECO1), called ctf7-1 and ctf7-2. Mutants exhibited dwarfism, poor anther development and sterility. Analysis of somatic tissues by flow cytometry, scanning electron microscopy and quantitative real-time PCR identified defects in DNA repair and cell division, including an increase in the area of leaf epidermal cells, an increase in DNA content and the upregulation of genes involved in DNA repair including BRCA1 and PARP2. No significant change was observed in the expression of genes that influence entry into the endocycle. Analysis of meiocytes identified changes in chromosome morphology and defective segregation; the abundance of chromosomal-bound cohesion subunits was also reduced. Transcript levels for several meiotic genes, including the recombinase genes DMC1 and RAD51C and the S-phase licensing factor CDC45 were elevated in mutant anthers. Taken together our results demonstrate that Arabidopsis CTF7/ECO1 plays important roles in the preservation of genome integrity and meiosis.
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    • "Arabidopsis CTF7 is required for microsporogenesis 3 situation previously observed in mutations for human ESCO2 (Vega et al., 2005). "
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    ABSTRACT: Proper transmission of DNA in dividing cells is crucial for the survival of eukaryotic organisms. During cell division, faithful segregation of replicated chromosomes requires their tight attachment, known as sister chromatid cohesion, until anaphase. Sister chromatid cohesion is established during S-phase in a process that requires an acetyltransferase that in yeast is known as Establishment of cohesion 1 (Eco1). Inactivation of Eco1 typically disrupts chromosome segregation and homologous recombination dependent DNA repair in dividing cells ultimately resulting in lethality. We report here the isolation and detailed characterization of two homozygous T-DNA insertion mutants for the Arabidopsis thaliana Eco1 homologue, CHROMOSOME TRANSMISSION FIDELITY 7/ ESTABLISHMENT OF COHESION 1 (CTF7/ECO1), called ctf7-1 and ctf7-2. Mutants exhibited dwarfism, poor anther development and sterility. Analysis of somatic tissues by flow cytometry, scanning electron microscopy and QPCR identified defects in DNA repair and cell division, including an increase in the area of leaf epidermal cells, an increase in DNA content, and the upregulation of genes involved in DNA repair including BRCA1 and PARP2. No significant change was observed in the expression of genes that influence entry into the endocycle. Analysis of meiocytes identified changes in chromosome morphology and defective segregation; the abundance of chromosomal-bound cohesion subunits was also reduced. Transcript levels for several meiotic genes, including the recombinase genes, DMC1 and RAD51C, and the S-phase licensing factor, CDC45 were elevated in mutant anthers. Taken together our results demonstrate that Arabidopsis CTF7/ECO1 plays important roles in preservation of genome integrity and meiosis. This article is protected by copyright. All rights reserved.
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