Functional importance and divergence of plant apurinic/apyrimidinic endonucleases in somatic and meiotic DNA repair
Functional importance and divergence of plant apurinic/apyrimidinic endonucleases in somatic and meiotic DNA repair
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DOI：
10.1093/plcell/koad056
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发表时间：
2023-03-15
期刊：
影响因子：
11.6
通讯作者：
Qian, Weiqiang
中科院分区：
文献类型：
--
作者：
Li, Jinchao;Wang, Cong;Qian, Weiqiang
Apurinic/apyrimidinic （AP）位点是最丰富的DNA损伤之一，主要由AP内切酶（ape）修复。虽然大多数真核生物基因组编码两个类人猿，但植物通常具有三个类人猿，即APE1L， APE2和ARP。迄今为止，植物类人猿的生物学相关性和功能分化尚不清楚。在这里，我们表明这三种植物类人猿有古老的起源，APE1L进化支是植物特异性的。在拟南芥（Arabidopsis thaliana）中，同时突变APE1L和APE2，但不是单独突变ARP或与APE1L或APE2联合突变，会导致与遗传毒性胁迫相关的明显发育缺陷。遗传分析表明，这三种类人猿在体内具有不同的底物偏好。ARP主要负责AP位点的修复，而APE1L和APE2更倾向于修复3 '阻断的单链DNA断裂。我们进一步确定类人猿在减数分裂细胞的DNA修复和基因组完整性维持中发挥重要作用。ape2双突变体的产孢1 （SPO11-1）依赖性和非SPO11-1依赖性双链DNA断裂频率显著提高。DNA损伤反应（DNA damage response， DDR）在ape1 ape2中被激活，导致花粉败育。本研究结果提示了植物类人猿的功能分化，揭示了植物类人猿在营养发育和生殖发育过程中的重要作用。拟南芥类人猿具有不同的底物偏好，并且需要体细胞和减数分裂细胞的基因组完整性。
Apurinic/apyrimidinic (AP) sites are one of the most abundant DNA lesions and are mainly repaired by AP endonucleases (APEs). While most eukaryotic genomes encode two APEs, plants usually possess three APEs, namely APE1L, APE2, and ARP. To date, the biological relevance and functional divergence of plant APEs are unclear. Here, we show that the three plant APEs have ancient origins, with the APE1L clade being plant-specific. In Arabidopsis thaliana, simultaneously mutating APE1L and APE2, but not ARP alone or in combination with either APE1L or APE2, results in clear developmental defects linked to genotoxic stress. Genetic analyses indicated that the three plant APEs have different substrate preferences in vivo. ARP is mainly responsible for AP site repair, while APE1L and APE2 prefer to repair 3 '-blocked single-stranded DNA breaks. We further determined that APEs play an important role in DNA repair and the maintenance of genomic integrity in meiotic cells. The ape1l ape2 double mutant exhibited a greatly enhanced frequency of sporulation 1 (SPO11-1)-dependent and SPO11-1-independent double-stranded DNA breaks. The DNA damage response (DDR) was activated in ape1l ape2 to trigger pollen abortion. Our findings suggest functional divergence of plant APEs and reveal important roles of plant APEs during vegetative and reproductive development.Arabidopsis APEs have different substrate preferences and are required for genomic integrity in somatic and meiotic cells.