共 68 条
Brca2-Pds5 complexes mobilize persistent meiotic recombination sites to the nuclear envelope
被引:18
作者:
Kusch, Thomas
[1
]
机构:
[1] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA
关键词:
Homologous recombination;
Brca2;
Pds5;
Cohesin;
Nuclear envelope;
Lamin;
DROSOPHILA-MELANOGASTER FEMALES;
DOUBLE-STRAND-BREAK;
SYNAPTONEMAL COMPLEX;
DNA-REPAIR;
HOMOLOGOUS RECOMBINATION;
ELECTRON-MICROSCOPY;
MAMMALIAN MEIOSIS;
VARIANT EXCHANGE;
GENE-EXPRESSION;
WILD-TYPE;
D O I:
10.1242/jcs.159988
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
Homologous recombination is required for reciprocal exchange between homologous chromosome arms during meiosis. Only select meiotic recombination events become chromosomal crossovers; the majority of recombination outcomes are noncrossovers. Growing evidence suggests that crossovers are repaired after noncrossovers. Here, I report that persisting recombination sites are mobilized to the nuclear envelope of Drosophila pro-oocytes during mid-pachytene. Their number correlates with the average crossover rate per meiosis. Proteomic and interaction studies reveal that the recombination mediator Brca2 associates with lamin and the cohesion factor Pds5 to secure persistent recombination sites at the nuclear envelope. In Rad51(-/-) females, all persistent DNA breaks are directed to the nuclear envelope. By contrast, a reduction of Pds5 or Brca2 levels abolishes the movement and has a negative impact on crossover rates. The data suggest that persistent meiotic DNA double-strand breaks might correspond to crossovers, which are mobilized to the nuclear envelope for their repair. The identification of Brca2-Pds5 complexes as key mediators of this process provides a first mechanistic explanation for the contribution of lamins and cohesins to meiotic recombination.
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页码:717 / 727
页数:11
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