Phosphorylation of HORMA-domain protein HTP-3 at Serine 285 is dispensable for crossover formation.
Phosphorylation of HORMA-domain protein HTP-3 at Serine 285 is dispensable for crossover formation.
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DOI：
10.1093/g3journal/jkac079
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发表时间：
2022-05-06
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功能性配子的产生是通过减数分裂过程中多层次的、精心安排的一系列事件来完成的。在秀丽隐杆线虫种系中，含有HORMA结构域的蛋白HTP-3在染色体轴的建立和程序性DNA双链断裂的有效诱导中起关键作用，这两者对于交叉形成都是至关重要的。双链断裂允许在第一次减数分裂期间精确的染色体分离，因此是产生健康配子的基本要求。HORMAD蛋白的磷酸化依赖性调节在控制减数分裂染色体行为中起重要作用。在这里，我们记录了HTP-3中丝氨酸285处的磷酸化位点，该位点在减数分裂前期I期间组成性磷酸化。pHTP-3S 285定位与panHTP-3重叠，除了在经历生理性凋亡的细胞核中，其中pHTP-3不存在。令人惊讶的是，我们观察到HTP-3在S285处的磷酸化不依赖于控制线虫减数分裂进程的经典激酶。在减数分裂过程中，htp-3（S285 A）突变体显示RAD-51周转加快，但没有其他减数分裂异常。总之，这些数据表明，Ser 285磷酸化是独立的典型的减数分裂蛋白激酶，不调节HTP-3依赖的减数分裂过程。我们提出了一个模型，其中磷酸化的HTP-3发生通过非经典或冗余的减数分裂激酶和/或可能是多余的额外的磷酸化位点在体内的功能。
Generation of functional gametes is accomplished through a multilayered and finely orchestrated succession of events during meiotic progression. In the Caenorhabditis elegans germline, the HORMA-domain-containing protein HTP-3 plays pivotal roles for the establishment of chromosome axes and the efficient induction of programmed DNA double-strand breaks, both of which are crucial for crossover formation. Double-strand breaks allow for accurate chromosome segregation during the first meiotic division and therefore are an essential requirement for the production of healthy gametes. Phosphorylation-dependent regulation of HORMAD protein plays important roles in controlling meiotic chromosome behavior. Here, we document a phospho-site in HTP-3 at Serine 285 that is constitutively phosphorylated during meiotic prophase I. pHTP-3S285 localization overlaps with panHTP-3 except in nuclei undergoing physiological apoptosis, in which pHTP-3 is absent. Surprisingly, we observed that phosphorylation of HTP-3 at S285 is independent of the canonical kinases that control meiotic progression in nematodes. During meiosis, the htp-3(S285A) mutant displays accelerated RAD-51 turnover, but no other meiotic abnormalities. Altogether, these data indicate that the Ser285 phosphorylation is independent of canonical meiotic protein kinases and does not regulate HTP-3-dependent meiotic processes. We propose a model wherein phosphorylation of HTP-3 occurs through noncanonical or redundant meiotic kinases and/or is likely redundant with additional phospho-sites for function in vivo.
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