XPG: a multitasking genome caretaker

Alba Muniesa-Vargas; Arjan F. Theil; Cristina Ribeiro-Silva; Wim Vermeulen; Hannes Lans

doi:10.1007/s00018-022-04194-5

XPG: a multitasking genome caretaker

Alba Muniesa-Vargas, Arjan F. Theil, Cristina Ribeiro-Silva, Wim Vermeulen, Hannes Lans^*

^*Corresponding author for this work

Molecular Genetics

Research output: Contribution to journal › Review article › Academic › peer-review

13 Citations (Scopus)

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Abstract

The XPG/ERCC5 endonuclease was originally identified as the causative gene for Xeroderma Pigmentosum complementation group G. Ever since its discovery, in depth biochemical, structural and cell biological studies have provided detailed mechanistic insight into its function in excising DNA damage in nucleotide excision repair, together with the ERCC1–XPF endonuclease. In recent years, it has become evident that XPG has additional important roles in genome maintenance that are independent of its function in NER, as XPG has been implicated in protecting replication forks by promoting homologous recombination as well as in resolving R-loops. Here, we provide an overview of the multitasking of XPG in genome maintenance, by describing in detail how its activity in NER is regulated and the evidence that points to important functions outside of NER. Furthermore, we present the various disease phenotypes associated with inherited XPG deficiency and discuss current ideas on how XPG deficiency leads to these different types of disease.

Original language	English
Article number	166
Journal	Cellular and Molecular Life Sciences
Volume	79
Issue number	3
DOIs	https://doi.org/10.1007/s00018-022-04194-5
Publication status	Published - 1 Mar 2022

Bibliographical note

Funding Information:
This work was supported the European Research Council (advanced Grant 340988-ERC-ID), Erasmus MC (HDMA Grant), the Dutch Cancer Society (KWF Grant 10506) and the gravitation program CancerGenomiCs.nl from the Netherlands Organization for Scientific Research. Oncode Institute is partly financed by the Dutch Cancer Society.

Publisher Copyright: © 2022, The Author(s).

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s00018-022-04194-5Final published version, 1.12 MBLicence: CC BY

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title = "XPG: a multitasking genome caretaker",

abstract = "The XPG/ERCC5 endonuclease was originally identified as the causative gene for Xeroderma Pigmentosum complementation group G. Ever since its discovery, in depth biochemical, structural and cell biological studies have provided detailed mechanistic insight into its function in excising DNA damage in nucleotide excision repair, together with the ERCC1–XPF endonuclease. In recent years, it has become evident that XPG has additional important roles in genome maintenance that are independent of its function in NER, as XPG has been implicated in protecting replication forks by promoting homologous recombination as well as in resolving R-loops. Here, we provide an overview of the multitasking of XPG in genome maintenance, by describing in detail how its activity in NER is regulated and the evidence that points to important functions outside of NER. Furthermore, we present the various disease phenotypes associated with inherited XPG deficiency and discuss current ideas on how XPG deficiency leads to these different types of disease.",

author = "Alba Muniesa-Vargas and Theil, {Arjan F.} and Cristina Ribeiro-Silva and Wim Vermeulen and Hannes Lans",

note = "Funding Information: This work was supported the European Research Council (advanced Grant 340988-ERC-ID), Erasmus MC (HDMA Grant), the Dutch Cancer Society (KWF Grant 10506) and the gravitation program CancerGenomiCs.nl from the Netherlands Organization for Scientific Research. Oncode Institute is partly financed by the Dutch Cancer Society. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Vermeulen, Wim

AU - Lans, Hannes

N1 - Funding Information: This work was supported the European Research Council (advanced Grant 340988-ERC-ID), Erasmus MC (HDMA Grant), the Dutch Cancer Society (KWF Grant 10506) and the gravitation program CancerGenomiCs.nl from the Netherlands Organization for Scientific Research. Oncode Institute is partly financed by the Dutch Cancer Society. Publisher Copyright: © 2022, The Author(s).

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N2 - The XPG/ERCC5 endonuclease was originally identified as the causative gene for Xeroderma Pigmentosum complementation group G. Ever since its discovery, in depth biochemical, structural and cell biological studies have provided detailed mechanistic insight into its function in excising DNA damage in nucleotide excision repair, together with the ERCC1–XPF endonuclease. In recent years, it has become evident that XPG has additional important roles in genome maintenance that are independent of its function in NER, as XPG has been implicated in protecting replication forks by promoting homologous recombination as well as in resolving R-loops. Here, we provide an overview of the multitasking of XPG in genome maintenance, by describing in detail how its activity in NER is regulated and the evidence that points to important functions outside of NER. Furthermore, we present the various disease phenotypes associated with inherited XPG deficiency and discuss current ideas on how XPG deficiency leads to these different types of disease.

AB - The XPG/ERCC5 endonuclease was originally identified as the causative gene for Xeroderma Pigmentosum complementation group G. Ever since its discovery, in depth biochemical, structural and cell biological studies have provided detailed mechanistic insight into its function in excising DNA damage in nucleotide excision repair, together with the ERCC1–XPF endonuclease. In recent years, it has become evident that XPG has additional important roles in genome maintenance that are independent of its function in NER, as XPG has been implicated in protecting replication forks by promoting homologous recombination as well as in resolving R-loops. Here, we provide an overview of the multitasking of XPG in genome maintenance, by describing in detail how its activity in NER is regulated and the evidence that points to important functions outside of NER. Furthermore, we present the various disease phenotypes associated with inherited XPG deficiency and discuss current ideas on how XPG deficiency leads to these different types of disease.

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JO - Cellular and Molecular Life Sciences

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ER -

XPG: a multitasking genome caretaker

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