Response to “XPA is primarily cytoplasmic but is transported into the nucleus upon UV damage”

Wood, Richard D.; Manandhar, Mandira; Lowery, Megan G.; Boulware, Karen S.; Lin, Kevin; Lu, Yao

doi:10.1016/j.dnarep.2018.01.002

Cited by 3 publications

(2 citation statements)

References 15 publications

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“…XPA is predominantly located in the nucleus in the G2-phase cell population with or without UV irradiation. The discrepancy between the reports on XPA localization is possibly due to a difference in the experimental methodology [ 119 , 120 ].…”

Section: The Ways To Control Xpamentioning

confidence: 99%

The XPA Protein—Life under Precise Control

Krasikova

Lavrik

Rechkunova

2022

Cells

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Nucleotide excision repair (NER) is a central DNA repair pathway responsible for removing a wide variety of DNA-distorting lesions from the genome. The highly choreographed cascade of core NER reactions requires more than 30 polypeptides. The xeroderma pigmentosum group A (XPA) protein plays an essential role in the NER process. XPA interacts with almost all NER participants and organizes the correct NER repair complex. In the absence of XPA’s scaffolding function, no repair process occurs. In this review, we briefly summarize our current knowledge about the XPA protein structure and analyze the formation of contact with its protein partners during NER complex assembling. We focus on different ways of regulation of the XPA protein’s activity and expression and pay special attention to the network of post-translational modifications. We also discuss the data that is not in line with the currently accepted hypothesis about the functioning of the XPA protein.

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Section: The Ways To Control Xpamentioning

confidence: 99%

The XPA Protein—Life under Precise Control

Krasikova

Lavrik

Rechkunova

2022

Cells

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“…Both poorly structured Nand C-terminal regions provide the XPA protein with flexibility important for its interaction with multiple partners. The N-terminus accommodates a nuclear localization signal (NLS); however, the question is still open as to whether XPA resides in the nucleus, or whether it is normally resident in the cytoplasm and is imported into the nucleus only after DNA damage [40][41][42][43]. Cellular localization of XPA is discussed in more detail in the text below.…”

Section: Introduction and Nucleotide Excision Repairmentioning

confidence: 99%

XPA: DNA Repair Protein of Significant Clinical Importance

Pulzová¹,

Ward

Chovanec³

2020

IJMS

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The nucleotide excision repair (NER) pathway is activated in response to a broad spectrum of DNA lesions, including bulky lesions induced by platinum-based chemotherapeutic agents. Expression levels of NER factors and resistance to chemotherapy has been examined with some suggestion that NER plays a role in tumour resistance; however, there is a great degree of variability in these studies. Nevertheless, recent clinical studies have suggested Xeroderma Pigmentosum group A (XPA) protein, a key regulator of the NER pathway that is essential for the repair of DNA damage induced by platinum-based chemotherapeutics, as a potential prognostic and predictive biomarker for response to treatment. XPA functions in damage verification step in NER, as well as a molecular scaffold to assemble other NER core factors around the DNA damage site, mediated by protein–protein interactions. In this review, we focus on the interacting partners and mechanisms of regulation of the XPA protein. We summarize clinical oncology data related to this DNA repair factor, particularly its relationship with treatment outcome, and examine the potential of XPA as a target for small molecule inhibitors.

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