Palindromic sequences can form hairpin and cruciform structures that pose a threat to genome integrity. We found that a 160-bp palindrome (an inverted repeat of 80 bp) conferred a mitotic recombination hotspot relative to a control nonpalindromic sequence when inserted into the ade6 gene of Schizosaccharomyces pombe. The hotspot activity of the palindrome, but not the basal level of recombination, was abolished by a rad50 deletion, by a rad50S "separation of function" mutation, or by a rad32-D25A mutation in the nuclease domain of the Rad32 protein, an Mre11 homolog. We propose that upon extrusion of the palindrome the Rad50.Rad32 nuclease complex recognizes and cleaves the secondary structure thus formed and generates a recombinogenic break in the DNA.
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http://dx.doi.org/10.1093/genetics/161.1.461 | DOI Listing |
Hematology
June 2016
a Istituto di Genetica e Biofisica "Adriano Buzzati-Traverso" - CNR , Napoli , Italy.
Objective And Importance: To verify the presence of β-thalassemia in subjects showing hematologic phenotype of α-thalassemia, conduct normal molecular sequence analysis of the α-globin genes, and detect the absence of the most frequent α-thalassemia deletions.
Clinical Presentation: A patient from Apulia (Southern Italy) was referred to our institution for the occasional founding of hypochromic polyglobulia and microcytic red blood cells associated with normal levels of Hb A2 and Hb F and normal iron parameters.
Intervention And Technique: The patient has been investigated using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), quantitative real-time PCR, restriction analysis, and gap-PCR.
Eur J Haematol
March 2013
Istituto di Genetica e Biofisica Adriano Buzzati-Traverso, Consiglio Nazionale delle Ricerche, Napoli, Italy.
Objectives: To characterize the molecular basis of a β-thalassemia defect in subjects with mild microcytosis associated with normal Hb A2 and increased levels of Hb F.
Methods: Six subjects from three apparently unrelated families from Campania (southern Italy) have been investigated using DNA restriction analysis, inverse PCR, cloning, sequencing, multiplex ligation-dependent probe amplification (MLPA), quantitative real-time PCR, and gap-PCR.
Results: We have identified a novel 55-kb β-globin gene cluster deletion in three unrelated families: the Italian (G) γ((A) γδβ)°-thalassemia.
Genes Genet Syst
April 2007
Department of Biology, The Hong Kong University of Science & Technology, Kowloon, Hong Kong SAR, China.
Extremely long PCR fragments were generated by PCR amplification of ITS and 5.8S rDNA from Cochlodinium polykrikoides against other dinoflagellates. These patterns were consistent among geographically different isolates of C.
View Article and Find Full Text PDFGenetics
March 2005
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
DNA palindromes are rare in humans but are associated with meiosis-specific translocations. The conserved Mre11/Rad50/Nbs1 (MRN) complex is likely directly involved in processing palindromes through the homologous recombination pathway of DNA repair. Using the fission yeast Schizosaccharomyces pombe as a model system, we show that a 160-bp palindrome (M-pal) is a meiotic recombination hotspot and is preferentially eliminated by gene conversion.
View Article and Find Full Text PDFBr J Haematol
October 2003
Department of Haematological Medicine, King's College Hospital, Guy's, Kings' & St Thomas' School of Medicine, King's College London, London, UK.
We describe a novel deletion causing (epsilongammadeltabeta) degrees thalassaemia segregating in three generations of a Chilean family of Spanish descent. Heterozygotes for the deletion were all affected by neonatal haemolytic anaemia. The deletion of 152,569 bp extends from 77 kb upstream of the epsilon gene to 31 kb downstream of the beta gene, and includes the entire beta-globin gene cluster and two upstream olfactory receptor genes.
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