Unlabelled: Repairing DNA double-strand breaks is crucial for maintaining genome integrity, which occurs primarily through homologous recombination (HR) in Nucleosomes, composed of DNA wrapped around a histone octamer, present a natural barrier to end-resection to initiate HR, but the impact on the downstream HR steps of homology search, DNA strand invasion and repair synthesis remain to be determined. Displacement loops (D-loops) play a pivotal role in HR, yet the influence of chromatin dynamics on D-loop metabolism remains unclear. Using the physical D-loop capture (DLC) and D-loop extension (DLE) assays to track HR intermediates, we employed genetic analysis to reveal that H2B mono-ubiquitylation (H2Bubi) affects multiple steps during HR repair. We infer that H2Bubi modulates chromatin structure, not only promoting histone degradation for nascent D-loop formation but also stabilizing extended D-loops through nucleosome assembly. Furthermore, H2Bubi regulates DNA resection Rad9 recruitment to suppress a feedback control mechanism that dampens D-loop formation and extension at hyper-resected ends. Through physical and genetic assays to determine repair outcomes, we demonstrate that H2Bubi plays a crucial role in preventing break-induced replication and thus promoting genomic stability.
Highlights: H2Bubi is epistatic to H2A.Z and INO80 in promoting homology search and D-loop formationH2Bubi stabilizes extended D-loopExcessive resection counteracts D-loop formation and extensionH2Bubi promotes crossover events and limits the frequency of break-induced replication outcomes in HR repair.
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http://dx.doi.org/10.1101/2024.09.13.612919 | DOI Listing |
PeerJ
December 2024
College of Animal Science and Technology, China Agricultural University, Beijing, China.
Mitochondria play a pivotal role as carriers of genetic information through their circular DNA molecules. The rapid evolution of the D-loop region in mitochondria makes it an ideal molecular marker for exploring genetic differentiation among individuals within species and populations with close kinship. However, the influence of mtDNA D-loop region haplotypes and mtDNA copy numbers on phenotypic traits, particularly production traits in chickens, remains poorly understood.
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December 2024
Laboratorio de Biología Acuática, Facultad de Biología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
Background: Understanding the processes that influence distribution of organisms is a major goal in evolutionary biology. Speciation in freshwater fishes is mainly associated with the "island-like" model of evolution, in which the formation of land barriers between different hydrographic basins interrupts gene flow and promotes isolation. Freshwater fish therefore provide an excellent model system for macro- and micro-evolutionary studies.
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December 2024
Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada.
The type IV pilus is a diverse molecular machine capable of conferring a variety of functions and is produced by a wide range of bacterial species. The ability of the pilus to perform host-cell adherence makes it a viable target for the development of vaccines against infection by human pathogens such as Pseudomonas aeruginosa. Here, the 1.
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December 2024
Laboratory for Environmental and Life Sciences, University of Nova Gorica, Vipavska 13, SI-500, Nova Gorica, Slovenia. Electronic address:
The Helicase-Like Transcription Factor (HLTF) is member of the SWI/SNF-family of ATP dependent chromatin remodellers known primarily for maintaining genome stability. Biochemical and cellular assays support its multiple roles in DNA Damage Tolerance. However, the lack of sufficient structural data limits the comprehension of the molecular basis of its modes of action.
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January 2025
Department of Neuroendocrinology, ICMR-National Institute for Research in Reproductive and Child Health, Parel, Mumbai, 400012, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address:
Varicocele has been associated with reduced male fertility potential. Treatment modalities for varicocele improve semen parameters, yet more than 50% of cases remain infertile. Varicocele-induced heat and hypoxia stress may affect sperm mitochondrial functions, possibly leading to aberrant epigenetic modifications.
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