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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. M. Kutuzov ◽  
E. A. Belousova ◽  
T. A. Kurgina ◽  
A. A. Ukraintsev ◽  
I. A. Vasil’eva ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Dependent Manner ◽  
Nucleosome Core ◽  
Nucleosome Core Particles ◽  
Significant Stimulation ◽  
Cellular Signal ◽  
Last Stage ◽  
Base Excision ◽  
Stimulation Of

AbstractThe regulation of repair processes including base excision repair (BER) in the presence of DNA damage is implemented by a cellular signal: poly(ADP-ribosyl)ation (PARylation), which is catalysed by PARP1 and PARP2. Despite ample 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, DNA polymerase β [Polβ] and DNA ligase IIIα [LigIIIα]) in combination with BER scaffold protein XRCC1 in the nucleosomal context. We constructed nucleosome core particles 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, Polβ and to a lesser extent LigIIIα. PARylation by PARP1 attenuated this effect to various degrees depending on the enzyme. PARP2 had an influence predominantly on the last stage of BER: DNA sealing. Nonetheless, PARylation by PARP2 led to Polβ inhibition and to significant stimulation of LigIIIα activities in a NAD+-dependent manner. On the basis of the obtained and literature data, we suggest a hypothetical model of the contribution of PARP1 and PARP2 to BER.

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

2020 ◽  
Author(s):  
M.M. Kutuzov ◽  
E.A. Belousova ◽  
T.A. Kurgina ◽  
A.A. Ukraintsev ◽  
I.A. Vasil’eva ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Dependent Manner ◽  
Repair Processes ◽  
Significant Stimulation ◽  
Cellular Signal ◽  
Last Stage ◽  
Base Excision ◽  
Stimulation Of

ABSTRACTThe 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, Polβ and LigIIIα) 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, Polβ, and to a lesser extent LigIIIα. 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 Polβ inhibition and to significant stimulation of LigIIIα activities in a NAD+-dependent manner.

scholarly journals Histones participate in base excision repair of 8-oxodGuo by transiently cross-linking with active repair intermediates in nucleosome core particles

2020 ◽  
Author(s):  
Mengtian Ren ◽  
Mengdi Shang ◽  
Huawei Wang ◽  
Zhen Xi ◽  
Chuanzheng Zhou
Keyword(s):  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Cross Linking ◽  
Nucleosome Core ◽  
Nucleosome Core Particles ◽  
Lyase Activity ◽  
Base Excision ◽  
Ap Lyase ◽  
Core Particles

Abstract 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) is a biomarker of oxidative DNA damage and can be repaired by hOGG1 and APE1 via the base excision repair (BER) pathway. In this work, we studied coordinated BER of 8-oxodGuo by hOGG1 and APE1 in nucleosome core particles and found that histones transiently formed DNA-protein cross-links (DPCs) with active repair intermediates such as 3′-phospho-α,β-unsaturated aldehyde (PUA) and 5′-deoxyribosephosphate (dRP). The effects of histone participation could be beneficial or deleterious to the BER process, depending on the circumstances. In the absence of APE1, histones enhanced the AP lyase activity of hOGG1 by cross-linking with 3′-PUA. However, the formed histone-PUA DPCs hampered the subsequent repair process. In the presence of APE1, both the AP lyase activity of hOGG1 and the formation of histone-PUA DPCs were suppressed. In this case, histones could catalyse removal of the 5′-dRP by transiently cross-linking with the active intermediate. That is, histones promoted the repair by acting as 5′-dRP lyases. Our findings demonstrate that histones participate in multiple steps of 8-oxodGuo repair in nucleosome core particles, highlighting the diverse roles that histones may play during DNA repair in eukaryotic cells.

scholarly journals Stimulation of NEIL2-mediated Oxidized Base Excision Repair via YB-1 Interaction during Oxidative Stress

2007 ◽  
Vol 282 (39) ◽  
pp. 28474-28484 ◽  
Author(s):  
Soumita Das ◽  
Ranajoy Chattopadhyay ◽  
Kishor K. Bhakat ◽  
Istvan Boldogh ◽  
Kimitoshi Kohno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Base Excision ◽  
Stimulation Of

scholarly journals Long Patch Base Excision Repair proceeds via coordinated stimulation of the multienzyme repair complex

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Lata Balakrishnan ◽  
Patrick Brandt ◽  
Laura Lindsey‐Boltz ◽  
Aziz Sancar ◽  
Robert Bambara
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Base Excision ◽  
Stimulation Of

Role of metformin on base excision repair pathway in p53 wild-type H2009 and HepG2 cancer cells

2017 ◽  
Vol 37 (9) ◽  
pp. 909-919 ◽  
Author(s):  
Irem Dogan Turacli ◽  
Tuba Candar ◽  
Berrin Emine Yuksel ◽  
Selda Demirtas
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Base Excision Repair ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Single Agent ◽  
Tumor Formation ◽  
Dna Base Excision Repair ◽  
Cellular Signal ◽  
Base Excision

The antidiabetic agent metformin was shown to further possess chemopreventive and chemotherapeutic effects against cancer. Despite the advances, the underlying molecular mechanisms involved in decreasing tumor formation are still unclear. The understanding of the participation of oxidative stress in the action mechanism of metformin and its related effects on p53 and on DNA base excision repair (BER) system can help us to get closer to solve metformin puzzle in cancer. We investigated the effects of metformin in HepG2 and H2009 cells, verifying cytotoxicity, oxidative stress, antioxidant status, and DNA BER system. Our results showed metformin induced oxidative stress and reduced antioxidant capacity. Also, metformin treatment with hydrogen peroxide (H2O2) enhanced these effects. Although DNA BER enzyme activities were not changed accordantly together by metformin as a single agent or in combination with H2O2, activated p53 was decreased with increased oxidative stress in H2009 cells. Our study on the relationship between metformin/reactive oxygen species and DNA BER system in cancer cells would be helpful to understand the anticancer effects of metformin through cellular signal transduction pathways. These findings can be a model of the changes on oxidative stress that reflects p53’s regulatory role on DNA repair systems in cancer for the future studies.

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