Lebedeva Natalia A, Rechkunova Nadejda I, Endutkin Anton V, Lavrik Olga I
Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia.
Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.
Front Cell Dev Biol. 2021 Jan 11;8:617301. doi: 10.3389/fcell.2020.617301. eCollection 2020.
Bifunctional 8-oxoguanine-DNA glycosylase (OGG1), a crucial DNA-repair enzyme, removes from DNA 8-oxo-7,8-dihydroguanine (8-oxoG) with following cleavage of the arising apurinic/apyrimidinic (AP) site. The major enzyme in eukaryotic cells that catalyzes the cleavage of AP sites is AP endonuclease 1 (APE1). Alternatively, AP sites can be cleaved by tyrosyl-DNA phosphodiesterase 1 (TDP1) to initiate APE1-independent repair, thus expanding the ability of the base excision repair (BER) process. Poly(ADP-ribose) polymerase 1 (PARP1) is a regulatory protein of DNA repair. PARP2 is also activated in response to DNA damage and can be regarded as the BER participant. Here we analyze PARP1 and PARP2 interactions with DNA intermediates of the initial stages of the BER process (8-oxoG and AP-site containing DNA) and their interplay with the proteins recognizing and processing these DNA structures focusing on OGG1. OGG1 as well as PARP1 and PARP2 form covalent complex with AP site-containing DNA without borohydride reduction. AP site incision by APE1 or TDP1 removal of protein adducts but not proteins' PARylation prevent DNA-protein crosslinks.
双功能8-氧代鸟嘌呤-DNA糖基化酶（OGG1）是一种关键的DNA修复酶，它从DNA中去除8-氧代-7,8-二氢鸟嘌呤（8-氧代鸟嘌呤），随后切割产生的无嘌呤/无嘧啶（AP）位点。真核细胞中催化AP位点切割的主要酶是AP核酸内切酶1（APE1）。另外，AP位点可被酪氨酰-DNA磷酸二酯酶1（TDP1）切割，以启动不依赖APE1的修复，从而扩展碱基切除修复（BER）过程的能力。聚（ADP-核糖）聚合酶1（PARP1）是DNA修复的一种调节蛋白。PARP2也会在DNA损伤时被激活，可被视为BER参与者。在此，我们分析PARP1和PARP2与BER过程初始阶段的DNA中间体（含8-氧代鸟嘌呤和AP位点的DNA）的相互作用，以及它们与识别和处理这些DNA结构的蛋白质（重点是OGG1）的相互作用。OGG1以及PARP1和PARP2在不进行硼氢化还原的情况下与含AP位点的DNA形成共价复合物。APE1切割AP位点或TDP1去除蛋白质加合物而非蛋白质的PAR化可防止DNA-蛋白质交联。
