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Poly(ADP-ribose) glycohydrolase coordinates meiotic DNA double-strand break induction and repair independent of its catalytic activity
Nature Communications ( IF 14.7 ) Pub Date : 2020-09-25 , DOI: 10.1038/s41467-020-18693-1
Eva Janisiw 1, 2 , Marilina Raices 3 , Fabiola Balmir 3, 4 , Luis F Paulin 5 , Antoine Baudrimont 1 , Arndt von Haeseler 5, 6 , Judith L Yanowitz 3 , Verena Jantsch 1 , Nicola Silva 7
Affiliation  

Poly(ADP-ribosyl)ation is a reversible post-translational modification synthetized by ADP-ribose transferases and removed by poly(ADP-ribose) glycohydrolase (PARG), which plays important roles in DNA damage repair. While well-studied in somatic tissues, much less is known about poly(ADP-ribosyl)ation in the germline, where DNA double-strand breaks are introduced by a regulated program and repaired by crossover recombination to establish a tether between homologous chromosomes. The interaction between the parental chromosomes is facilitated by meiotic specific adaptation of the chromosome axes and cohesins, and reinforced by the synaptonemal complex. Here, we uncover an unexpected role for PARG in coordinating the induction of meiotic DNA breaks and their homologous recombination-mediated repair in Caenorhabditis elegans. PARG-1/PARG interacts with both axial and central elements of the synaptonemal complex, REC-8/Rec8 and the MRN/X complex. PARG-1 shapes the recombination landscape and reinforces the tightly regulated control of crossover numbers without requiring its catalytic activity. We unravel roles in regulating meiosis, beyond its enzymatic activity in poly(ADP-ribose) catabolism.



中文翻译:

聚(ADP-核糖)糖水解酶协调减数分裂 DNA 双链断裂诱导和修复,与其催化活性无关

聚(ADP-核糖基)化是一种可逆的翻译后修饰,由 ADP-核糖转移酶合成并被聚(ADP-核糖)糖水解酶 (PARG) 去除,在 DNA 损伤修复中起重要作用。虽然在体细胞组织中进行了充分研究,但对种系中的聚 (ADP-核糖基) 化知之甚少,其中 DNA 双链断裂由受监管的程序引入,并通过交叉重组修复以在同源染色体之间建立系链。染色体轴和粘连蛋白的减数分裂特异性适应促进了亲代染色体之间的相互作用,并通过联会复合体得到加强。在这里,我们发现了 PARG 在协调减数分裂 DNA 断裂的诱导及其在秀丽隐杆线虫中的同源重组介导的修复中的意外作用. PARG-1/PARG 与联会复合体、REC-8/Rec8 和 MRN/X 复合体的轴向和中心元素相互作用。PARG-1 塑造了重组格局,并加强了对交叉数的严格控制,而不需要其催化活性。我们揭示了在调节减数分裂中的作用,超越了其在聚(ADP-核糖)分解代谢中的酶活性。

更新日期:2020-09-25
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