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Review
. 2022 Aug;49(8):7995-8006.
doi: 10.1007/s11033-022-07324-1. Epub 2022 May 20.

XPG in the Nucleotide Excision Repair and Beyond: a study on the different functional aspects of XPG and its associated diseases

Riasha Pal  1 , Nilanjan Paul  1 , Deep Bhattacharya  1 , Sudeshna Rakshit  1 , Geetha Shanmugam  1 , Koustav Sarkar  2
Affiliations
Review

XPG in the Nucleotide Excision Repair and Beyond: a study on the different functional aspects of XPG and its associated diseases

Riasha Pal et al. Mol Biol Rep. 2022 Aug.

Erratum in

Abstract

Several proteins are involved in DNA repair mechanisms attempting to repair damages to the DNA continuously. One such protein is Xeroderma Pigmentosum Complementation Group G (XPG), a significant component in the Nucleotide Excision Repair (NER) pathway. XPG is accountable for making the 3' incision in the NER, while XPF-ERCC4 joins ERCC1 to form the XPF-ERCC1 complex. This complex makes a 5' incision to eliminate bulky DNA lesions. XPG is also known to function as a cofactor in the Base Excision Repair (BER) pathway by increasing hNth1 activity, apart from its crucial involvement in the NER. Reports suggest that XPG also plays a non-catalytic role in the Homologous Recombination Repair (HRR) pathway by forming higher-order complexes with BRCA1, BRCA2, Rad51, and PALB2, further influencing the activity of these molecules. Studies show that, apart from its vital role in repairing DNA damages, XPG is also responsible for R-loop formation, which facilitates exhibiting phenotypes of Werner Syndrome. Though XPG has a role in several DNA repair pathways and molecular mechanisms, it is primarily a NER protein. Unrepaired and prolonged DNA damage leads to genomic instability and facilitates neurological disorders, aging, pigmentation, and cancer susceptibility. This review explores the vital role of XPG in different DNA repair mechanisms which are continuously involved in repairing these damaged sites and its failure leading to XP-G, XP-G/CS complex phenotypes, and cancer progression.

Keywords: Base excision repair; Homologous recombination repair, R-loops; Nucleotide excision repair; Xeroderma Pigmentosum complementation group G.

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