Meiotic DNA break repair can utilize homolog-independent chromatid templates in C. elegans.
Meiotic DNA break repair can utilize homolog-independent chromatid templates in C. elegans.
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DOI：
10.1016/j.cub.2021.03.008
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发表时间：
2021-04-12
期刊：
影响因子：
--
通讯作者：
Libuda DE
中科院分区：
文献类型：
--
作者：
Toraason E;Horacek A;Clark C;Glover ML;Adler VL;Premkumar T;Salagean A;Cole F;Libuda DE
在减数分裂期间，维持基因组的完整性对于产生可存活的单倍体配子至关重要。在减数分裂前期I，双链DNA断裂（DSB）被诱导，这些DSB的一个子集被修复为同源物间的交换，以确保正确的染色体分离。不能作为与同源物的交叉而解析的DSB必须通过其他途径修复以确保基因组完整性。为了确定替代修复模板是否可以在卵子发生过程中参与减数分裂DSB修复，我们开发了一种检测秀丽隐杆线虫减数分裂过程中定义的DSB位点处的姐妹和/或染色单体内修复事件的测定法。使用这种方法，我们直接证明了姐妹染色单体或相同的DNA分子可以作为减数分裂修复模板进行交叉和非交叉重组，非交叉事件是主要的重组结果。我们还发现，姐妹或染色单体内底物可作为整个减数分裂前期I诱导的DSB的重组伴侣，包括后期前期时，同源物不可用。非交叉转换道序列的分析表明，DSB的处理类似于整个前期I。我们进一步提出的数据表明，XPF-1核酸酶的功能在后期前期促进姐妹或染色单体内修复的步骤后，联合分子加工重组。尽管它在姐妹或染色单体内修复的功能，我们发现，xpf-1突变体并没有表现出严重的缺陷，暴露于电离辐射的后代的生存能力。总的来说，我们建议C。elegans XPF-1可能仅在后期前期I中作为intersister或染色单体内消退酶起辅助作用。Toraason等人开发了一种测定法，该测定法建立并表征了单个诱导的DNA双链断裂与姐妹染色单体或相同的DNA分子在C.优美的这项研究也证明了XPF-1核酸酶在后期减数分裂前期I促进同源物非依赖性修复的作用。
During meiosis, the maintenance of genome integrity is critical for generating viable haploid gametes. In meiotic prophase I, double-strand DNA breaks (DSBs) are induced and a subset of these DSBs are repaired as interhomolog crossovers to ensure proper chromosome segregation. DSBs not resolved as crossovers with the homolog must be repaired by other pathways to ensure genome integrity. To determine if alternative repair templates can be engaged for meiotic DSB repair during oogenesis, we developed an assay to detect sister and/or intra-chromatid repair events at a defined DSB site during Caenorhabditis elegans meiosis. Using this assay, we directly demonstrate that the sister chromatid or the same DNA molecule can be engaged as a meiotic repair template for both crossover and noncrossover recombination, with noncrossover events being the predominant recombination outcome. We additionally find that the sister or intra-chromatid substrate is available as a recombination partner for DSBs induced throughout meiotic prophase I, including late prophase when the homolog is unavailable. Analysis of noncrossover conversion tract sequences reveals that DSBs are processed similarly throughout prophase I. We further present data indicating that the XPF-1 nuclease functions in late prophase to promote sister or intra-chromatid repair at steps of recombination following joint molecule processing. Despite its function in sister or intra-chromatid repair, we find that xpf-1 mutants do not exhibit severe defects in progeny viability following exposure to ionizing radiation. Overall, we propose that C. elegans XPF-1 may assist as an intersister or intrachromatid resolvase only in late prophase I. Toraason et al. develop an assay that both establishes and characterizes repair of a single induced DNA double-strand break with the sister chromatid or same DNA molecule in C. elegans. This study also demonstrates a role for the XPF-1 nuclease in promoting homolog-independent repair during late meiotic prophase I.
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影响因子：
4.5
作者：
Agostinho A;Meier B;Sonneville R;Jagut M;Woglar A;Blow J;Jantsch V;Gartner A
通讯作者：
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DOI：
10.1073/pnas.0406157101
发表时间：
2004-11-02
影响因子：
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作者：
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DOI：
10.1126/science.1191125
发表时间：
2010-07-02
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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