TY - JOUR

T1 - XPA

T2 - DNA repair protein of significant clinical importance

AU - Pulzová, L.B.

AU - Ward, T.A.

AU - Chovanec, M.

PY - 2020/3/22

Y1 - 2020/3/22

N2 - 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.

AB - 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.

KW - Biomarker

KW - Cancer

KW - Nucleotide excision repair

KW - Prognostic and predictive value

KW - Single nucleotide polymorphism

KW - Small molecule inhibitors

KW - XPA protein

KW - double stranded DNA

KW - hypoxia inducible factor 1alpha

KW - nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1

KW - transcription factor

KW - xeroderma pigmentosum group A protein

KW - acute myeloid leukemia

KW - cancer chemotherapy

KW - cancer growth

KW - cancer incidence

KW - cancer prognosis

KW - cancer therapy

KW - carcinogenesis

KW - cell proliferation

KW - colorectal cancer

KW - DNA binding

KW - DNA damage response

KW - DNA repair

KW - DNA strand breakage

KW - energy metabolism

KW - human

KW - leukemia

KW - malignant neoplasm

KW - molecularly targeted therapy

KW - oxidative phosphorylation

KW - protein phosphorylation

KW - regulatory mechanism

KW - Review

KW - signal transduction

KW - transcription regulation

KW - treatment outcome

KW - tumor growth

KW - ubiquitination

KW - xeroderma pigmentosum

U2 - 10.3390/ijms21062182

DO - 10.3390/ijms21062182

M3 - Journal article

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 6

M1 - 2182

ER -