The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context

Published: Oct. 5, 2020, 7:01 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.05.325944v1?rss=1 Authors: Kutuzov, M., Belousova, E., Kurgina, T., Ukraintsev, A., Vasil'eva, I., Khodyreva, S., Lavrik, O. Abstract: The repair processes regulation including base excision repair (BER) is implemented by a cellular signal PARylation catalysed by PARP1 and PARP2. Despite intensive studies, it is far from clear how BER is regulated by PARPs and how the roles are distributed between the PARPs. Here, we investigated the effects of PARP1, PARP2 and PARylation on activities of the main BER enzymes (APE1, Polbeta and LigIIIalfa) in combination with XRCC1 in the nucleosomal context. We constructed nucleosomes with midward- or outward-oriented damage. It was concluded that in most cases, the presence of PARP1 leads to the suppression of the activities of APE1, Polbeta, and to a lesser extent LigIIIalfa. PARylation by PARP1 attenuated this effect to various degrees. PARP2 had an influence predominantly on the last stage of BER: DNA sealing. Nonetheless, PARylation by PARP2 led to Polbeta inhibition and to significant stimulation of LigIIIalfa activities in a NAD+-dependent manner. Copy rights belong to original authors. Visit the link for more info