Recombination-independent recognition of DNA homology for meiotic silencing in Neurospora crassa.
Recombination-independent recognition of DNA homology for meiotic silencing in Neurospora crassa.
复制标题
粗糙脉孢菌减数分裂沉默 DNA 同源性的重组独立识别。
DOI：
10.1073/pnas.2108664118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Gladyshev,Eugene
中科院分区：
文献类型：
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作者：
Rhoades,Nicholas;Nguyen,Tinh-Suong;Witz,Guillaume;Cecere,Germano;Hammond,Thomas;Mazur,AlexeyK;Gladyshev,Eugene
同源染色体的配对代表了几乎所有有性生殖物种减数分裂的关键步骤。在许多生物体中，配对涉及表面上保持完整的染色体。基于这种配对的同源识别的机械性质尚不清楚。使用“不配对DNA减数分裂沉默”（MSUD）作为模型过程，我们证明了减数分裂中存在一种截然不同的DNA同源性识别方法。 MSUD 相对于其他实验系统的主要优势在于它能够识别任何缺乏同源等位基因伴侣的相对较短的 DNA 片段。在这里，我们表明 MSUD 不依赖于减数分裂重组的经典机制，但它是由减数分裂凝聚复合体的保守成分 REC8 促进的。我们还表明，某些散布同源模式在 MSUD 过程中被认为是可配对的。此类模式必须是共线的，并且必须包含以 21 或 22 个碱基对间隔的序列同一性短片段。通过使用这些周期性值作为全原子分子建模中的指导参数，我们发现同源 DNA 分子可以通过形成间隔为 2.5 个螺旋圈的四链体接触来配对。这个过程需要右手螺旋卷绕和中间双螺旋段的额外构象变化。我们的结果 1) 调和了遗传和生物物理证据，证明直接同源双链 DNA (dsDNA)-dsDNA 配对的存在，2) 确定了该过程在启动 RNA 干扰中的作用，3) 表明染色体可以通过作用于完整 dsDNA 分子的精确机制进行交叉匹配。
The pairing of homologous chromosomes represents a critical step of meiosis in nearly all sexually reproducing species. In many organisms, pairing involves chromosomes that remain apparently intact. The mechanistic nature of homology recognition at the basis of such pairing is unknown. Using “meiotic silencing by unpaired DNA” (MSUD) as a model process, we demonstrate the existence of a cardinally different approach to DNA homology recognition in meiosis. The main advantage of MSUD over other experimental systems lies in its ability to identify any relatively short DNA fragment lacking a homologous allelic partner. Here, we show that MSUD does not rely on the canonical mechanism of meiotic recombination, yet it is promoted by REC8, a conserved component of the meiotic cohesion complex. We also show that certain patterns of interspersed homology are recognized as pairable during MSUD. Such patterns need to be colinear and must contain short tracts of sequence identity spaced apart at 21 or 22 base pairs. By using these periodicity values as a guiding parameter in all-atom molecular modeling, we discover that homologous DNA molecules can pair by forming quadruplex-based contacts with an interval of 2.5 helical turns. This process requires right-handed plectonemic coiling and additional conformational changes in the intervening double-helical segments. Our results 1) reconcile genetic and biophysical evidence for the existence of direct homologous double-stranded DNA (dsDNA)–dsDNA pairing, 2) identify a role for this process in initiating RNA interference, and 3) suggest that chromosomes can be cross-matched by a precise mechanism that operates on intact dsDNA molecules.