XPC deficiency is related to APE1 and OGG1 expression and function

Melo, Julliane Tamara Araújo de; Timóteo, Ana Rafaela de Souza; Lajus, Tirzah Braz Petta; Brandão, Juliana Alves; Souza-Pinto, Nadja C. de; Menck, Carlos Frederico Martins; Campalans, Anna; Radicella, J. Pablo; Vessoni, Alexandre Teixeira; Muotri, Alysson R.; Agnez-Lima, Lucymara Fassarella

doi:10.1016/j.mrfmmm.2016.01.004

Cited by 15 publications

(12 citation statements)

References 53 publications

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“…In agreement with our results, it has been shown that XPC is recruited to 8-oxoguanine lesions to induce a partial removal of the oxidative DNA damage and regulate cellular stress-response (Zhou et al, 2001;Miccoli et al, 2007). This is done by stimulating OGG1's protein expression and catalytic activity and physically interacting with APE1 (D'Errico et al, 2006;De Melo et al, 2016). Hence, XPC mutation affects them directly.…”

Section: Downregulation Of Different Ber-associated Gene and Protein supporting

confidence: 91%

Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage

et al. 2020

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Xeroderma Pigmentosum C (XPC) is a multi-functional protein that is involved not only in the repair of bulky lesions, post-irradiation, via nucleotide excision repair (NER) per se but also in oxidative DNA damage mending. Since base excision repair (BER) is the primary regulator of oxidative DNA damage, we characterized, post-Ultraviolet B-rays (UVB)-irradiation, the detailed effect of three different XPC mutations in primary fibroblasts derived from XP-C patients on mRNA, protein expression and activity of different BER factors. We found that XP-C fibroblasts are characterized by downregulated expression of different BER factors including OGG1, MYH, APE1, LIG3, XRCC1, and Polβ. Such a downregulation was also observed at OGG1, MYH, and APE1 protein levels. This was accompanied with an increase in DNA oxidative lesions, as evidenced by 8-oxoguanine levels, immediately post-UVB-irradiation. Unlike in normal control cells, these oxidative lesions persisted over time in XP-C cells having lower excision repair capacities. Taken together, our results indicated that an impaired BER pathway in XP-C fibroblasts leads to longer persistence and delayed repair of oxidative DNA damage. This might explain the diverse clinical phenotypes in XP-C patients suffering from cancer in both photo-protected and photo-exposed areas. Therapeutic strategies based on reinforcement of BER pathway might therefore represent an innovative path for limiting the drawbacks of NER-based diseases, as in XP-C case.

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Section: Downregulation Of Different Ber-associated Gene and Protein supporting

confidence: 91%

Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage

et al. 2020

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“…XPC also stimulates OGG1 binding to damaged DNA, and a weak interaction between the proteins was obtained from far western analysis (Parlanti et al, 2012). Finally, Melo et al (2016) showed a correlation between XPC deficiency and OGG1/ APE1 expression levels, and a physical interaction between XPC and APE1 using co-immunoprecipitation. These studies are summarized in Tables 1 and 2. Oxidized guanine lesions are excised more efficiently by competing BER than NER pathways…”

Section: Oxidatively Generated Base Damage Recognized By Ner Pathwaymentioning

confidence: 91%

“…XPC-HR23B and TDG Shimizu et al (2003) XPC and OGG1 D' Errico et al (2006) XPC and APE1/OGG1 Melo et al (2016) (Sp) and 5-guanidinohydantoin (Gh), which are recognized by the DNA glycosylase NEIL1 (Luo et al, 2000;Niles et al, 2001;Hailer et al, 2005;Krishnamurthy et al, 2008;Zhao et al, 2010). Very recently, Shafirovich et al (2019) examined the excision of these lesions in intact human cells and the relative contribution of BER and NER in the processing of these lesions.…”

Section: Protein-protein Interaction Referencesmentioning

confidence: 99%

Cooperation and interplay between base and nucleotide excision repair pathways: From DNA lesions to proteins

et al. 2020

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Base and nucleotide excision repair (BER and NER) pathways are normally associated with removal of specific types of DNA damage: small base modifications (such as those induced by DNA oxidation) and bulky DNA lesions (such as those induced by ultraviolet or chemical carcinogens), respectively. However, growing evidence indicates that this scenario is much more complex and these pathways exchange proteins and cooperate with each other in the repair of specific lesions. In this review, we highlight studies discussing the involvement of NER in the repair of DNA damage induced by oxidative stress, and BER participating in the removal of bulky adducts on DNA. Adding to this complexity, UVA light experiments revealed that oxidative stress also causes protein oxidation, directly affecting proteins involved in both NER and BER. This reduces the cell's ability to repair DNA damage with deleterious implications to the cells, such as mutagenesis and cell death, and to the organisms, such as cancer and aging. Finally, an interactome of NER and BER proteins is presented, showing the strong connection between these pathways, indicating that further investigation may reveal new functions shared by them, and their cooperation in maintaining genome stability.

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“…Furthermore, NTHL1 mutations or deficiencies are associated with multi-cancer phenotype including colorectal cancer and breast cancer 22 . In addition, nucleotide excision repair (NER) protein XPC may regulate OGG1 expression and participates in BER pathway to repair oxidative DNA damage, suggesting crosstalk between different DNA repair pathways 23,24 .…”

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confidence: 99%

Genomic alterations and abnormal expression of APE2 in multiple cancers

Jensen

Shi

Shan

2020

Sci Rep

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Although APE2 plays essential roles in base excision repair and ATR-Chk1 DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients. Here, we report multiple-cancer analyses of APE2 genomic alterations and mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We observe that APE2 genomic alterations occur at ~17% frequency in 14 cancer types (n = 21,769). Most frequent somatic mutations of APE2 appear in uterus (2.89%) and skin (2.47%) tumor samples. Furthermore, APE2 expression is upregulated in tumor tissue compared with matched nonmalignant tissue across 5 cancer types including kidney, breast, lung, liver, and uterine cancers, but not in prostate cancer. We also examine the mRNA expression of 13 other DNA repair and DDR genes from matched samples for 6 cancer types. We show that APE2 mRNA expression is positively correlated with PCNA, APE1, XRCC1, PARP1, Chk1, and Chk2 across these 6 tumor tissue types; however, groupings of other DNA repair and DDR genes are correlated with APE2 with different patterns in different cancer types. Taken together, this study demonstrates alterations and abnormal expression of APE2 from multiple cancers.

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XPC deficiency is related to APE1 and OGG1 expression and function

Cited by 15 publications

References 53 publications

Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage

Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage

Cooperation and interplay between base and nucleotide excision repair pathways: From DNA lesions to proteins

Genomic alterations and abnormal expression of APE2 in multiple cancers

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