Sepšiová Regina, Procházková Katarína, Červenák Filip, Majerčík Denis, Hanáková Kateřina, Lattová Erika, Hajikazemi Mona, Zdráhal Zbyněk, Virágová Sofia, Brzáčová Zuzana, Paeschke Katrin, Nosek Jozef, Tomáška Ľubomír
Department of Genetics, Comenius University Bratislava, Faculty of Natural Sciences, Ilkovičova 6, 842 15 Bratislava, Slovakia.
Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Nucleic Acids Res. 2025 Sep 5;53(17). doi: 10.1093/nar/gkaf837.
Poly (ADP-ribose) polymerases (PARPs) are enzymes catalyzing the post-translational addition of chains of ADP-ribose moieties to proteins. In most eukaryotic cells, their primary protein targets are involved in DNA recombination, repair, and chromosome maintenance. Even though this group of enzymes is quite common in both eukaryotes and prokaryotes, no PARP homologs have been described so far in ascomycetous yeasts, leaving their potential roles in this group of organisms unexplored. Here, we characterize Pyl1 protein of Yarrowia lipolytica as the first candidate of PARP in yeasts. We show that the expression of PYL1 gene is increased in mutants lacking either subunit of telomerase and identified several of its candidate protein targets in vivo. We demonstrate that Pyl1p is a functional PARP that undergoes auto-PARylation and PARylates YlKu70/80 complex. We also show that overexpression of PYL1 in Y. lipolytica cells results in dissociation of YlKu80 from telomeres in vivo, supporting the role of Pyl1p in telomere protection and maintenance. Based on our observations, we propose Pyl1p and its homologs identified in other yeast species represent a distinct class of PARPs, thus substantiating a more detailed investigation of their roles in these organisms.
聚（ADP - 核糖）聚合酶（PARP）是一类能够催化将ADP - 核糖部分的链翻译后添加到蛋白质上的酶。在大多数真核细胞中，它们的主要蛋白质靶点参与DNA重组、修复和染色体维持。尽管这类酶在真核生物和原核生物中都相当常见，但迄今为止在子囊菌酵母中尚未发现PARP同源物，其在这类生物体中的潜在作用仍未被探索。在此，我们将解脂耶氏酵母的Pyl1蛋白鉴定为酵母中PARP的首个候选蛋白。我们发现，在缺乏端粒酶任一亚基的突变体中，PYL1基因的表达会增加，并在体内鉴定出其几个候选蛋白靶点。我们证明Pyl1p是一种功能性PARP，它会发生自身PAR化并使YlKu70/80复合物PAR化。我们还表明，在解脂耶氏酵母细胞中过表达PYL1会导致YlKu80在体内从端粒上解离，这支持了Pyl1p在端粒保护和维持中的作用。基于我们的观察结果，我们提出在其他酵母物种中鉴定出的Pyl1p及其同源物代表了一类独特的PARP，从而证实有必要对它们在这些生物体中的作用进行更详细的研究。
