Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis

Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis

Summary: Assembly and disassembly of DNA repair protein complexes at DNA damage sites are essential for maintaining genomic integrity. Investigating factors coordinating assembly of the base excision repair (BER) proteins DNA polymerase β (Polβ) and XRCC1 to DNA lesion sites identifies a role for Po...

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Autores principales: Christopher A. Koczor, Kate M. Saville, Joel F. Andrews, Jennifer Clark, Qingming Fang, Jianfeng Li, Rasha Q. Al-Rahahleh, Md Ibrahim, Steven McClellan, Mikhail V. Makarov, Marie E. Migaud, Robert W. Sobol
Formato: article
Lenguaje:EN
Publicado: Elsevier 2021
Materias:
DNA polymerase β
XRCC1
poly(ADP-ribose)
PAR
NAD+
NRH
Biology (General)
QH301-705.5
Acceso en línea:https://doaj.org/article/6a82efe53d94463fb399bda39a6d5f71
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spelling oai:doaj.org-article:6a82efe53d94463fb399bda39a6d5f712021-11-04T04:29:06ZTemporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis2211-124710.1016/j.celrep.2021.109917https://doaj.org/article/6a82efe53d94463fb399bda39a6d5f712021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013905https://doaj.org/toc/2211-1247Summary: Assembly and disassembly of DNA repair protein complexes at DNA damage sites are essential for maintaining genomic integrity. Investigating factors coordinating assembly of the base excision repair (BER) proteins DNA polymerase β (Polβ) and XRCC1 to DNA lesion sites identifies a role for Polβ in regulating XRCC1 disassembly from DNA repair complexes and, conversely, demonstrates Polβ’s dependence on XRCC1 for complex assembly. LivePAR, a genetically encoded probe for live-cell imaging of poly(ADP-ribose) (PAR), reveals that Polβ and XRCC1 require PAR for repair-complex assembly, with PARP1 and PARP2 playing unique roles in complex dynamics. Further, BER complex assembly is modulated by attenuation/augmentation of NAD+ biosynthesis. Finally, SIRT6 does not modulate PARP1 or PARP2 activation but does regulate XRCC1 recruitment, leading to diminished Polβ abundance at sites of DNA damage. These findings highlight coordinated yet independent roles for PARP1, PARP2, and SIRT6 and their regulation by NAD+ bioavailability to facilitate BER.Christopher A. KoczorKate M. SavilleJoel F. AndrewsJennifer ClarkQingming FangJianfeng LiRasha Q. Al-RahahlehMd IbrahimSteven McClellanMikhail V. MakarovMarie E. MigaudRobert W. SobolElsevierarticleDNA polymerase βXRCC1poly(ADP-ribose)PARNAD+NRHBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109917- (2021)
institution DOAJ
collection DOAJ
language EN
topic DNA polymerase β
XRCC1
poly(ADP-ribose)
PAR
NAD+
NRH
Biology (General)
QH301-705.5
spellingShingle DNA polymerase β
XRCC1
poly(ADP-ribose)
PAR
NAD+
NRH
Biology (General)
QH301-705.5
Christopher A. Koczor
Kate M. Saville
Joel F. Andrews
Jennifer Clark
Qingming Fang
Jianfeng Li
Rasha Q. Al-Rahahleh
Md Ibrahim
Steven McClellan
Mikhail V. Makarov
Marie E. Migaud
Robert W. Sobol
Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis
description Summary: Assembly and disassembly of DNA repair protein complexes at DNA damage sites are essential for maintaining genomic integrity. Investigating factors coordinating assembly of the base excision repair (BER) proteins DNA polymerase β (Polβ) and XRCC1 to DNA lesion sites identifies a role for Polβ in regulating XRCC1 disassembly from DNA repair complexes and, conversely, demonstrates Polβ’s dependence on XRCC1 for complex assembly. LivePAR, a genetically encoded probe for live-cell imaging of poly(ADP-ribose) (PAR), reveals that Polβ and XRCC1 require PAR for repair-complex assembly, with PARP1 and PARP2 playing unique roles in complex dynamics. Further, BER complex assembly is modulated by attenuation/augmentation of NAD+ biosynthesis. Finally, SIRT6 does not modulate PARP1 or PARP2 activation but does regulate XRCC1 recruitment, leading to diminished Polβ abundance at sites of DNA damage. These findings highlight coordinated yet independent roles for PARP1, PARP2, and SIRT6 and their regulation by NAD+ bioavailability to facilitate BER.
format article
author Christopher A. Koczor
Kate M. Saville
Joel F. Andrews
Jennifer Clark
Qingming Fang
Jianfeng Li
Rasha Q. Al-Rahahleh
Md Ibrahim
Steven McClellan
Mikhail V. Makarov
Marie E. Migaud
Robert W. Sobol
author_facet Christopher A. Koczor
Kate M. Saville
Joel F. Andrews
Jennifer Clark
Qingming Fang
Jianfeng Li
Rasha Q. Al-Rahahleh
Md Ibrahim
Steven McClellan
Mikhail V. Makarov
Marie E. Migaud
Robert W. Sobol
author_sort Christopher A. Koczor
title Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis
title_short Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis
title_full Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis
title_fullStr Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis
title_full_unstemmed Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis
title_sort temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the parp/nad+/sirt6 axis
publisher Elsevier
publishDate 2021
url https://doaj.org/article/6a82efe53d94463fb399bda39a6d5f71
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