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Excess crossovers impede faithful meiotic chromosome segregation in C. elegans.
PLOS Genetics ( IF 4.0 ) Pub Date : 2020-09-04 , DOI: 10.1371/journal.pgen.1009001
Jeremy A Hollis 1 , Marissa L Glover 2 , Aleesa J Schlientz 2 , Cori K Cahoon 2 , Bruce Bowerman 2 , Sarah M Wignall 1 , Diana E Libuda 2
Affiliation  

During meiosis, diploid organisms reduce their chromosome number by half to generate haploid gametes. This process depends on the repair of double strand DNA breaks as crossover recombination events between homologous chromosomes, which hold homologs together to ensure their proper segregation to opposite spindle poles during the first meiotic division. Although most organisms are limited in the number of crossovers between homologs by a phenomenon called crossover interference, the consequences of excess interfering crossovers on meiotic chromosome segregation are not well known. Here we show that extra interfering crossovers lead to a range of meiotic defects and we uncover mechanisms that counteract these errors. Using chromosomes that exhibit a high frequency of supernumerary crossovers in Caenorhabditis elegans, we find that essential chromosomal structures are mispatterned in the presence of multiple crossovers, subjecting chromosomes to improper spindle forces and leading to defects in metaphase alignment. Additionally, the chromosomes with extra interfering crossovers often exhibited segregation defects in anaphase I, with a high incidence of chromatin bridges that sometimes created a tether between the chromosome and the first polar body. However, these anaphase I bridges were often able to resolve in a LEM-3 nuclease dependent manner, and chromosome tethers that persisted were frequently resolved during Meiosis II by a second mechanism that preferentially segregates the tethered sister chromatid into the polar body. Altogether these findings demonstrate that excess interfering crossovers can severely impact chromosome patterning and segregation, highlighting the importance of limiting the number of recombination events between homologous chromosomes for the proper execution of meiosis.



中文翻译:

过多的交换阻碍了秀丽隐杆线虫的忠实减数分裂染色体分离。

在减数分裂期间,二倍体生物将其染色体数目减少一半,从而产生单倍体配子。这个过程取决于双链DNA断裂的修复,这是同源染色体之间的交叉重组事件,它们将同源物保持在一起,以确保它们在第一次减数分裂过程中正确地分离到相反的纺锤极。尽管大多数生物通过称为交叉干扰的现象限制了同源物之间的交叉数量,但是,过度干扰交叉对减数分裂染色体分离的后果尚不清楚。在这里,我们表明额外的干扰交叉会导致一系列减数分裂缺陷,并且我们发现了抵消这些错误的机制。使用在秀丽隐杆线虫中表现出高频率交叉交换的染色体,我们发现在多个交叉的存在下基本染色体结构的图谱错误,使染色体受到不适当的纺锤体力并导致中期对准中的缺陷。另外,具有额外干扰的染色体通常在后期I中表现出分离缺陷,染色质桥的发生率很高,有时会在染色体和第一个极体之间形成系链。但是,这些后期I桥通常能够以LEM-3核酸酶依赖的方式进行分解,并且在减数分裂II期间,通过优先将被束缚的姊妹染色单体分离到极体中的第二种机制,持久存在的染色体系链经常被解析。总而言之,这些发现表明,过多的干扰交叉会严重影响染色体的模式和分离,

更新日期:2020-09-05
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