During meiosis, the formation of viable haploid gametes from diploid precursors requires that each homologous chromosome pair be properly segregated to produce an exact haploid set of chromosomes. Genetic recombination, which provides a physical connection between homologous chromosomes, is essential in most species for proper homologue segregation. Nevertheless, recombination is repressed specifically in and around the centromeres of chromosomes, apparently because rare centromeric (or pericentromeric) recombination events, when they do occur, can disrupt proper segregation and lead to genetic disabilities, including birth defects. The basis by which centromeric meiotic recombination is repressed has been largely unknown. We report here that, in fission yeast, RNAi functions and Clr4-Rik1 (histone H3 lysine 9 methyltransferase) are required for repression of centromeric recombination. Surprisingly, one mutant derepressed for recombination in the heterochromatic mating-type region during meiosis and several mutants derepressed for centromeric gene expression during mitotic growth are not derepressed for centromeric recombination during meiosis. These results reveal a complex relation between types of repression by heterochromatin. Our results also reveal a previously undemonstrated role for RNAi and heterochromatin in the repression of meiotic centromeric recombination and, potentially, in the prevention of birth defects by maintenance of proper chromosome segregation during meiosis.
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http://dx.doi.org/10.1073/pnas.0914160107 | DOI Listing |
Nature
January 2025
deCODE genetics/Amgen Inc., Reykjavik, Iceland.
Human recombination maps are a valuable resource for association and linkage studies and crucial for many inferences of population history and natural selection. Existing maps are based solely on cross-over (CO) recombination, omitting non-cross-overs (NCOs)-the more common form of recombination-owing to the difficulty in detecting them. Using whole-genome sequence data in families, we estimate the number of NCOs transmitted from parent to offspring and derive complete, sex-specific recombination maps including both NCOs and COs.
View Article and Find Full Text PDFNat Commun
January 2025
Instituto de Biología Funcional y Genómica, Zacarías González 2, Salamanca, 37007, Spain.
Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet.
View Article and Find Full Text PDFClin Pediatr Endocrinol
January 2025
Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
Solitary median maxillary central incisor (SMMCI) syndrome, the mildest form of the holoprosencephaly spectrum, is a rare anomaly characterized by the presence of a single midline central incisor in both the deciduous and permanent dentitions. Affected individuals can present with additional midline defects beyond dental findings. The 22q11.
View Article and Find Full Text PDFbioRxiv
December 2024
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
The centromere effect (CE) is a meiotic phenomenon that ensures meiotic crossover suppression in pericentromeric regions. Despite being a critical safeguard against nondisjunction, the mechanisms behind the CE remain unknown. Previous studies have shown that various regions of the pericentromere, encompassing proximal euchromatin, beta and alpha heterochromatin, undergo varying levels of crossover suppression, raising the question of whether distinct mechanisms establish the CE in these different regions.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular and Cellular Biology, Harvard University, Cambridge MA, USA.
In meiosis, one round of DNA replication followed by two rounds of chromosome segregation halves the ploidy of the original cell. Accurate chromosome segregation in meiosis I depends on recombination between homologous chromosomes. Sister centromeres attach to the same spindle pole in this division and only segregate in meiosis II.
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