A long non-coding RNA is required for targeting centromeric protein A to the human centromere. CENP-A chromatin disassembly in stressed and senescent murine cells. Hédouin, S., Grillo, G., Ivkovic, I., Velasco, G. Temporal and spatial uncoupling of DNA double strand break repair pathways within mammalian heterochromatin. A breakpoint map of recurrent chromosomal rearrangements in human neoplasia. Jumping translocations are common in solid tumor cell lines and result in recurrent fusions of whole chromosome arms: Jumping Translocations in Solid Tumors. A mechanism for the suppression of homologous recombination in G1 cells. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. Centromere fission, not telomere erosion, triggers chromosomal instability in human carcinomas. The molecular basis for centromere identity and function. The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA. Our results support a model in which licensing of homologous recombination at centromeric breaks occurs throughout the cell cycle to prevent the activation of mutagenic DNA repair pathways and preserve centromeric integrity.īarra, V. Finally, we show that inhibition of homologous recombination in G1 leads to centromeric instability and chromosomal translocations. CENP-A and HJURP interact with the deubiquitinase USP11, enabling formation of the RAD51–BRCA1–BRCA2 complex 5 and rendering the centromeres accessible to RAD51 recruitment and homologous recombination in G1. H3K4me2 promotes DNA-end resection by allowing DNA damage-induced centromeric transcription and increased formation of DNA–RNA hybrids. Mechanistically, we show that the centromere-specific histone H3 variant CENP-A and its chaperone HJURP, together with dimethylation of lysine 4 in histone 3 (H3K4me2), enable a succession of events leading to the licensing of homologous recombination in G1.
Here we demonstrate that DNA breaks that occur at centromeres in G1 recruit the homologous recombination machinery, despite the absence of a sister chromatid. DNA repair by homologous recombination requires the presence of the sister chromatid and is suppressed in the G1 phase of the cell cycle 4.
Although they are intrinsically fragile and represent hotspots for chromosomal rearrangements 3, little is known about how centromere integrity in response to DNA damage is preserved. Centromeres have unique chromatin features that are essential for centromere maintenance 2. Centromeric integrity is key for proper chromosome segregation during cell division 1.