Nucleosome Core Particles Lacking H2B or H3 Tails Are Altered Structurally and Have Differential Base Excision Repair Fingerprints

Biochemistry ◽  
2021 ◽  
Vol 60 (3) ◽  
pp. 210-218
Author(s):  
Paul J. Caffrey ◽  
Sarah Delaney
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Nucleosome Core ◽  
Nucleosome Core Particles ◽  
Base Excision ◽  
Core Particles

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 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 Chromatin and other obstacles to base excision repair: potential roles in carcinogenesis

Mutagenesis ◽  
2019 ◽  
Author(s):  
Paul J Caffrey ◽  
Sarah Delaney
Keyword(s):  
Base Excision Repair ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Histone Variants ◽  
Clinical Effects ◽  
Nucleosome Core ◽  
Biochemical Characterisation ◽  
Base Excision ◽  
Chemotherapeutic Treatment ◽  
Patient Prognosis

Abstract DNA is comprised of chemically reactive nucleobases that exist under a constant barrage from damaging agents. Failure to repair chemical modifications to these nucleobases can result in mutations that can cause various diseases, including cancer. Fortunately, the base excision repair (BER) pathway can repair modified nucleobases and prevent these deleterious mutations. However, this pathway can be hindered through several mechanisms. For instance, mutations to the enzymes in the BER pathway have been identified in cancers. Biochemical characterisation of these mutants has elucidated various mechanisms that inhibit their activity. Furthermore, the packaging of DNA into chromatin poses another obstacle to the ability of BER enzymes to function properly. Investigations of BER in the base unit of chromatin, the nucleosome core particle (NCP), have revealed that the NCP acts as a complex substrate for BER enzymes. The constituent proteins of the NCP, the histones, also have variants that can further impact the structure of the NCP and may modulate access of enzymes to the packaged DNA. These histone variants have also displayed significant clinical effects both in carcinogenesis and patient prognosis. This review focuses on the underlying molecular mechanisms that present obstacles to BER and the relationship of these obstacles to cancer. In addition, several chemotherapeutics induce DNA damage that can be repaired by the BER pathway and understanding obstacles to BER can inform how resistance and/or sensitivity to these therapies may occur. With the understanding of these molecular mechanisms, current chemotherapeutic treatment regiments may be improved, and future therapies developed.

Modulation of Base Excision Repair Alters Cellular Sensitivity to UVA1 but not to UVB¶

2002 ◽  
Vol 75 (5) ◽  
pp. 507 ◽  
Author(s):  
Katherine J. Kim ◽  
Indraneel Chakrabarty ◽  
Guang-Zhi Li ◽  
Sabine Grösch ◽  
Bernd Kaina ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Cellular Sensitivity ◽  
Base Excision

Defective Base Excision Repair Associated with NTHL1

2019 ◽  
Vol 68 ◽  
Author(s):  
Richarda de Voer ◽  
Paul W Doetsch ◽  
Roland Kuiper ◽  
Barbara Rivera
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Base Excision

A new DNA breaks repair pathway involving PARP3 and base excision repair proteins

2018 ◽  
Vol 482 (1) ◽  
pp. 96-100
Author(s):  
E. Belousova ◽  
◽  
M. Kutuzov ◽  
P. Ivankina ◽  
A. Ishchenko ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Pathway ◽  
Dna Breaks ◽  
Base Excision
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