The 3′–5′ DNA Exonuclease TREX1 Directly Interacts with Poly(ADP-ribose) Polymerase-1 (PARP1) during the DNA Damage Response

Miyazaki, Tatsuya; Kim, Yong Soo; Yoon, Jeongheon; Wang, Hongsheng; Suzuki, Tomohiko; Morse, Herbert C.

doi:10.1074/jbc.m114.547331

Cited by 40 publications

(32 citation statements)

References 41 publications

(57 reference statements)

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“…While TREX1 has not been considered a canonical DNA repair enzyme, recent studies highlight a broader role for this exonuclease. For example, TREX1 has been shown to interact with PARP and facilitates its nuclear localization and activity35. In addition to ssDNA, TREX1 has now been implicated in the degradation of dsDNA and ssRNA3637.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment

et al. 2016

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Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth. Mechanistically, miR-103 regulation of its target gene TREX1 in endothelial cells governs the secretion of pro-inflammatory cytokines into the tumour microenvironment. Our data suggest that this inflammatory milieu may potentiate tumour cell death by supporting immune activation and inducing tumour expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk between vasculature and tumour cells that can be exploited to improve the efficacy of chemotherapy and radiation.

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Section: Discussionmentioning

confidence: 99%

MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment

et al. 2016

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“…TREX1 from humans was reported to be involved in the DNA editing and repairing process. In several studies, it has been shown that TREX1 interacts with DNA polymerases to facilitate the polymerase accuracy [ 21 , 22 ]. Since the silencing of ICP35 gene by dsRNA reduced the viral copy number in the WSSV-infected shrimp, it has been speculated that the role of ICP35 might be involved in viral replication process [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

ICP35 Is a TREX-Like Protein Identified in White Spot Syndrome Virus

et al. 2016

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ICP35 is a non-structural protein from White spot syndrome virus believed to be important in viral replication. Since ICP35 was found to localize in the host nucleus, it has been speculated that the function of ICP35 might be involved in the interaction of DNA. In this study, we overexpressed, purified and characterized ICP35. The thioredoxin-fused ICP35 (thio-ICP35) was strongly expressed in E. coli and be able to form itself into dimers. Investigation of the interaction between ICP35 and DNA revealed that ICP35 can perform DNase activity. Structural model of ICP35 was successfully built on TREX1, suggesting that ICP35 might adopt the folding similar to that of TREX1 protein. Several residues important for dimerization in TREX1 are also conserved in ICP35. Residue Asn126 and Asp132, which are seen to be in close proximity to metal ions in the ICP35 model, were shown through site-directed mutagenesis to be critical for DNase activity.

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“…Additionally, it has been implicated in the regulation of BER through enhancing PARP1 [poly(ADP‐ribose) polymerase 1] activity. Moreover, TREX1 also possesses exoribonuclease activity and plays a role in the degradation of damaged tRNA substrates . Indeed, a large cohort of BER proteins have been implicated in RNA metabolism, and will be further discussed.…”

Section: Links Between the Ddr And Rna Metabolism Pathwaysmentioning

confidence: 97%

Dual roles of DNA repair enzymes in RNA biology/post‐transcriptional control

2016

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Despite consistent research into the molecular principles of the DNA damage repair pathway for almost two decades, it has only recently been found that RNA metabolism is very tightly related to this pathway, and the two ancient biochemical mechanisms act in alliance to maintain cellular genomic integrity. The close links between these pathways are well exemplified by examining the base excision repair pathway, which is now well known for dual roles of many of its members in DNA repair and RNA surveillance, including APE1, SMUG1, and PARP1. With additional links between these pathways steadily emerging, this review aims to provide a summary of the emerging roles for DNA repair proteins in the post-transcriptional regulation of RNAs. WIREs RNA 2016, 7:604-619. doi: 10.1002/wrna.1353 For further resources related to this article, please visit the WIREs website.

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The 3′–5′ DNA Exonuclease TREX1 Directly Interacts with Poly(ADP-ribose) Polymerase-1 (PARP1) during the DNA Damage Response

Cited by 40 publications

References 41 publications

MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment

MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment

ICP35 Is a TREX-Like Protein Identified in White Spot Syndrome Virus

Dual roles of DNA repair enzymes in RNA biology/post‐transcriptional control

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