Suppression of crossing-over by DNA methylation in Ascobolus

Suppression of crossing-over by DNA methylation in Ascobolus
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DOI:
10.1101/gad.12.9.1381
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发表时间:
1998-05-01
影响因子:
10.5
通讯作者:
Rossignol, JL
Rossignol, JL
中科院分区:
生物学1区
文献类型:
--
作者:
Maloisel, L;Rossignol, JL

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分散的DNA重复序列之间的同源重组产生对基因组有害的染色体重排。在许多真核生物中,与DNA重复序列相关的甲基化可能有助于抑制同源重组,并在保持基因组完整性方面发挥作用。我们已经测试了DNA甲基化抑制真菌Ascobolus immersus减数分裂重组的假设。利用自然的减数分裂前甲基化诱导过程(MIP)对b2孢子颜色基因(一个7.5kb的染色体重组热点)进行甲基化。当b2在两个同源物上被甲基化时,b2侧翼的两个标记之间的交换频率降低了几百倍。这表明DNA甲基化强烈抑制同源重组。当b2仅在一个同源物上甲基化时,交换仍然减少50倍,表明甲基化的作用不能限于阻断甲基化同源物上重组的起始。在这些和其他观察的基础上,我们提出,DNA甲基化干扰配对的两个完整的同源物之间的重组启动前和/或损害重组中间体的正常处理。
Homologous recombination between dispersed DNA repeats creates chromosomal rearrangements that are deleterious to the genome. The methylation associated with DNA repeats in many eukaryotes might serve to inhibit homologous recombination and play a role in preserving genome integrity. We have tested the hypothesis that DNA methylation suppresses meiotic recombination in the fungus Ascobolus immersus. The natural process of methylation-induced premeiotically (MIP) was used to methylate the b2 spore color gene, a 7.5-kb chromosomal recombination hot spot. The frequency of crossing-over between two markers flanking b2 was reduced several hundredfold when b2 was methylated on the two homologs. This demonstrates that DNA methylation strongly inhibits homologous recombination. When b2 was methylated on one homolog only, crossing-over was still reduced 50-fold, indicating that the effect of methylation cannot be limited to the blocking of initiation of recombination on the methylated homolog. On the basis of these and other observations, we propose that DNA methylation perturbs pairing between the two intact homologs before recombination initiation and/or impairs the normal processing of recombination intermediates.