X Chromosome Crossover Formation and Genome Stability inCaenorhabditis elegansAre Independently Regulated byxnd-1
| Autor: | Rana Mainpal, T. Brooke McClendon, Judith L. Yanowitz, Michael W. Krause, Francis Raj Gandhi Amrit, Arjumand Ghazi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genome instability X Chromosome DNA repair Investigations QH426-470 medicine.disease_cause Genomic Instability Chromosomal crossover Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine Radiation Ionizing Genetics medicine Animals meiosis DNA Breaks Double-Stranded Crossing Over Genetic Transgenes Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Alleles Genetics (clinical) Mutation biology Chromatin genome instability Fertility Germ Cells Phenotype 030104 developmental biology Histone Gene Expression Regulation Tip60 ATM biology.protein Germ line development ionizing radiation Homologous recombination 030217 neurology & neurosurgery |
| Zdroj: | G3: Genes, Genomes, Genetics, Vol 6, Iss 12, Pp 3913-3925 (2016) G3: Genes|Genomes|Genetics |
| ISSN: | 2160-1836 |
| Popis: | The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs, and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover (CO) distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understood. We have used the xnd-1 mutant of Caenorhabditis elegans to explore the relationship between genome integrity and crossover formation. Known for its role in ensuring X chromosome CO formation and germ line development, we show that xnd-1 also regulates genome stability. xnd-1 mutants exhibited a mortal germ line, high embryonic lethality, high incidence of males, and sensitivity to ionizing radiation. We discovered that a hypomorphic allele of mys-1 suppressed these genome instability phenotypes of xnd-1, but did not suppress the CO defects, suggesting it serves as a separation-of-function allele. mys-1 encodes a histone acetyltransferase, whose homolog Tip60 acetylates H2AK5, a histone mark associated with transcriptional activation that is increased in xnd-1 mutant germ lines, raising the possibility that thresholds of H2AK5ac may differentially influence distinct germ line repair events. We also show that xnd-1 regulated him-5 transcriptionally, independently of mys-1, and that ectopic expression of him-5 suppressed the CO defects of xnd-1. Our work provides xnd-1 as a model in which to study the link between chromatin factors, gene expression, and genome stability. |
| Databáze: | OpenAIRE |
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