The human apurinic/apyrimidinic endonuclease-1 suppresses activation of poly(adp-ribose) polymerase-1 induced by DNA single strand breaks

Peddi, Srinivasa R.; Chattopadhyay, Ranajoy; Naidu, C. V.; Izumi, Tohru

doi:10.1016/j.tox.2006.04.025

Cited by 31 publications

(22 citation statements)

References 76 publications

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“…For example, it has been implicated in nucleotide incision repair (NIR) (Wiederhold et al, 2004), involved in NK cell mediated killing through granzyme A (GzmA) (Fan et al, 2003;Martinvalet et al, 2005), prevents oxidative stress by negatively regulating Rac1/GTPase activity (Ozaki et al, 2002), regulates endothelial NO production and vascular tone (Jeon et al, 2004) and a recent finding that is important for our studies, Ape1/Ref-1 appears to suppress the activation of PARP1 (poly(ADP-ribose) polymerase 1) during the repair process of oxidative DNA damage, which may allow cells to avoid cell death (Peddi et al, 2006). Other findings of a relationship between Ape1/Ref-1 and Bcl2 levels (Jin et al, 2006) and Ape1/Ref-1's action as a negative regulator of the parathyroid hormone gene have been observed Chung et al, 1996;Kuninger et al, 2002;Okazaki et al, 1994).…”

Section: Other Functions Of Ape1/ref-1mentioning

confidence: 88%

The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target

Fishel¹,

Kelley²

2007

Molecular Aspects of Medicine

247

243

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Section: Other Functions Of Ape1/ref-1mentioning

confidence: 88%

The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target

Fishel¹,

Kelley²

2007

Molecular Aspects of Medicine

247

243

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“…For example, it is involved in NK-cell-mediated killing through granzyme A (GzmA) [93, 94], prevents oxidative stress by negatively regulating Rac1/GTPase activity [95], regulates endothelial NO production and vascular tone [96] and suppresses the activation of PARP1 during the repair of oxidative DNA damage [97]. Other findings include an inverse relationship between APE1 and Bcl2 levels [98] and its negative regulation of the parathyroid hormone gene and PTEN activator [99–103].…”

Section: Ape1’s Varied Functionsmentioning

confidence: 99%

APE1/Ref-1Role in Redox Signaling: Translational Applications of Targeting the Redox Function of the DNA Repair/Redox Protein APE1/Ref-1

Kelley¹,

Georgiadis²,

Fishel

2012

CMP

149

176

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The heterogeneity of most cancers diminishes the treatment effectiveness of many cancer-killing regimens. Thus, treatments that hold the most promise are ones that block multiple signaling pathways essential to cancer survival. One of the most promising proteins in that regard is APE1, whose reduction-oxidation activity influences multiple cancer survival mechanisms, including growth, proliferation, metastasis, angiogenesis, and stress responses. With the continued research using APE1 redox specific inhibitors alone or coupled with developing APE1 DNA repair inhibitors it will now be possible to further delineate the role of APE1 redox, repair and protein-protein interactions. Previously, use of siRNA or over expression approaches, while valuable, do not give a clear picture of the two major functions of APE1 since both techniques severely alter the cellular milieu. Additionally, use of the redox-specific APE1 inhibitor, APX3330, now makes it possible to study how inhibition of APE1’s redox signaling can affect multiple tumor pathways and can potentiate the effectiveness of existing cancer regimens. Because APE1 is an upstream effector of VEGF, as well as other molecules that relate to angiogenesis and the tumor microenvironment, it is also being studied as a possible treatment for age-related macular degeneration and diabetic retinopathy. This paper reviews all of APE1’s functions, while heavily focusing on its redox activities. It also discusses APE1’s altered expression in many cancers and the therapeutic potential of selective inhibition of redox regulation, which is the subject of intense preclinical studies.

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“…For instance, APE1 has been shown to inhibit the activation of PARP-1 during the response to DNA damage generated by oxidative stress, presumably by competing for binding to single-strand breaks, and as a result APE1 prevents apoptosis (31). APE1 is also involved in a caspase-independent cell death pathway potentially by serving as a substrate for granzyme A proteolytical inactivation (15), as well as in negative regulation of the parathyroid hormone gene by acting as a transcriptional repressor (8).…”

Section: General Description Of the Different Functions Of Ape1mentioning

confidence: 99%

Intrusion of a DNA Repair Protein in the RNome World: Is This the Beginning of a New Era?

Tell

Wilson

Lee

2010

Molecular and Cellular Biology

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3Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is known to be involved in base excision DNA repair, acting as the major abasic endonuclease; the protein also functions as a redox coactivator of several transcription factors that regulate gene expression. Recent findings highlight a novel role for APE1 in RNA metabolism. The new findings are as follows: (i) APE1 interacts with rRNA and ribosome processing protein NPM1 within the nucleolus; (ii) APE1 interacts with proteins involved in ribosome assembly (i.e., RLA0, RSSA) and RNA maturation (i.e., PRP19, MEP50) within the cytoplasm; (iii) APE1 cleaves abasic RNA; and (iv) APE1 cleaves a specific coding region of c-myc mRNA in vitro and influences c-myc mRNA level and half-life in cells. Such findings on the role of APE1 in the posttranscriptional control of gene expression could explain its ability to influence diverse biological processes and its relocalization to cytoplasmic compartments in some tissues and tumors. In addition, we propose that APE1 serves as a "cleansing" factor for oxidatively damaged abasic RNA, establishing a novel connection between DNA and RNA surveillance mechanisms. In this review, we introduce questions and speculations concerning the role of APE1 in RNA metabolism and discuss the implications of these findings in a broader evolutionary context.There is an emerging body of evidence that links DNA repair proteins to specific aspects of RNA metabolism. Currently, little is known about how cells cope with damaged RNA, either modified or oxidized, but it is clear that such RNA can impair protein synthesis, thus affecting cell function and viability. Specific surveillance mechanisms are therefore needed to remove damaged molecules from the RNA pool to guarantee the biological integrity of cells.The idea that quality control mechanisms might exist to repair RNA was brought to the forefront with the identification of the biochemical activities of the mammalian AlkB homologs. In particular, it was discovered that AlkB (from Escherichia coli) and the human homolog hABH3, besides being able to directly reverse alkylation damage on DNA bases, are able to demethylate damaged bases on RNA, thus playing a key role in the repair of specific RNA lesions (1, 30). While repair mechanisms have been demonstrated for alkylated RNA, such activity is not yet known for oxidatively damaged RNA. However, their existence seems improbable, in the absence of direct reversal strategies, due to the lack of a template for accurate repair, as in the case of double-stranded DNA. Since, under oxidative stress conditions, oxidation of RNA can occur up to a 10-to 20-fold-higher extent than oxidation of DNA (24), the question is: how is oxidized RNA specifically removed or repaired?The recent findings of Berquist et al. (7), Barnes et al. (4), and Vascotto et al. (39) highlight a novel "moonlighting" role for the repair apurinic/apyrimidinic (AP) endonuclease 1 (APE1) in RNA metabolism, both as a possible "cleansing" factor for damaged abasic ...

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The human apurinic/apyrimidinic endonuclease-1 suppresses activation of poly(adp-ribose) polymerase-1 induced by DNA single strand breaks

Cited by 31 publications

References 76 publications

The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target

The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target

APE1/Ref-1Role in Redox Signaling: Translational Applications of Targeting the Redox Function of the DNA Repair/Redox Protein APE1/Ref-1

Intrusion of a DNA Repair Protein in the RNome World: Is This the Beginning of a New Era?

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