The ADP-ribose hydrolase NUDT5 is important for DNA repair

Qi, Hongyun; Wright, Roni H. G.; Beato, Miguel; Price, Brendan D.

doi:10.1016/j.celrep.2022.111866

Cited by 11 publications

(5 citation statements)

References 47 publications

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“…Our experiments rule out unrestrained MARylation and PARylation reactions in response to zymosan and agree with the report of a fast recycling of ribose-5-phosphate and ADPr-derived AMP into the salvage route to replenish nuclear ATP [ 64 ]. However, the data do not allow an unambiguous characterization of the mechanism(s) of NAD + depletion.…”

Section: Discussionsupporting

confidence: 91%

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells

Alvarez,

Mancebo,

Alonso

et al. 2024

Redox Biology

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Section: Discussionsupporting

confidence: 91%

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells

Alvarez,

Mancebo,

Alonso

et al. 2024

Redox Biology

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“…A follow-up study by Pickup et al [ 16 ] demonstrated that breast cancer stem cells require the ATP-generating NUDT5 function to maintain cancer stemness. A recent study by Qi et al [ 35 ] emphasized the importance of NUDT5’s ATP-producing role at DNA damage sites. To evaluate the possibility of utilizing NUDT5 as a prognostic factor, Zhang et al [ 36 ] found that NUDT5 is highly expressed in breast cancer specimens, and patients with high NUDT5 expression have worse clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

The novel phosphatase NUDT5 is a critical regulator of triple-negative breast cancer growth

Qian,

Ma,

Tahaney

et al. 2024

Breast Cancer Res

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Background The most aggressive form of breast cancer is triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER) and progesterone receptor (PR), and does not have overexpression of the human epidermal growth factor receptor 2 (HER2). Treatment options for women with TNBC tumors are limited, unlike those with ER-positive tumors that can be treated with hormone therapy, or those with HER2-positive tumors that can be treated with anti-HER2 therapy. Therefore, we have sought to identify novel targeted therapies for TNBC. In this study, we investigated the potential of a novel phosphatase, NUDT5, as a potential therapeutic target for TNBC. Methods The mRNA expression levels of NUDT5 in breast cancers were investigated using TCGA and METABRIC (Curtis) datasets. NUDT5 ablation was achieved through siRNA targeting and NUDT5 inhibition with the small molecule inhibitor TH5427. Xenograft TNBC animal models were employed to assess the effect of NUDT5 inhibition on in vivo tumor growth. Proliferation, death, and DNA replication assays were conducted to investigate the cellular biological effects of NUDT5 loss or inhibition. The accumulation of 8-oxo-guanine (8-oxoG) and the induction of γH2AX after NUDT5 loss was determined by immunofluorescence staining. The impact of NUDT5 loss on replication fork was assessed by measuring DNA fiber length. Results In this study, we demonstrated the significant role of an overexpressed phosphatase, NUDT5, in regulating oxidative DNA damage in TNBCs. Our findings indicate that loss of NUDT5 results in suppressed growth of TNBC both in vitro and in vivo. This growth inhibition is not attributed to cell death, but rather to the suppression of proliferation. The loss or inhibition of NUDT5 led to an increase in the oxidative DNA lesion 8-oxoG, and triggered the DNA damage response in the nucleus. The interference with DNA replication ultimately inhibited proliferation. Conclusions NUDT5 plays a crucial role in preventing oxidative DNA damage in TNBC cells. The loss or inhibition of NUDT5 significantly suppresses the growth of TNBCs. These biological and mechanistic studies provide the groundwork for future research and the potential development of NUDT5 inhibitors as a promising therapeutic approach for TNBC patients.

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“…radiodurans has a total of 23 Nudix proteins and during the early stage of radiation recovery it strongly induces MutT (DR0261) along with four more nudix proteins [ 12 ]. A recent study in mammalian cell suggests that ADP-ribose hydrolase of NUDT5 motif helps in DNA repair in homologous recombination pathway as well as supply with ATP required for repair by hydrolysing ADP-ribose [ 103 ]. Using NCBI CD search we could find that each of the strains possesses an ADP-ribose hydrolase of NUDT5 motif (VITHBRA001_04428 and VITHBRA024_02687) which could also work for DNA damage repair in these strains.…”

Section: Resultsmentioning

confidence: 99%

Unraveling radiation resistance strategies in two bacterial strains from the high background radiation area of Chavara-Neendakara: A comprehensive whole genome analysis

Pal,

Yuvaraj,

Krishnan

et al. 2024

PLoS ONE

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This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial strains, Metabacillus halosaccharovorans (VITHBRA001) and Bacillus paralicheniformis (VITHBRA024) (D10 values 2.32 kGy and 1.42 kGy, respectively), inhabiting the top-ranking high background radiation area (HBRA) of Chavara-Neendakara placer deposit (Kerala, India). The present investigation has been carried out in the context that information on strategies of bacteria having mid-range resistance for gamma radiation is inadequate. WGS, annotation, COG and KEGG analyses and manual curation of genes helped us address the possible pathways involved in the major domains of radiation resistance, involving recombination repair, base excision repair, nucleotide excision repair and mismatch repair, and the antioxidant genes, which the candidate could activate to survive under ionizing radiation. Additionally, with the help of these data, we could compare the candidate strains with that of the extremely radiation resistant model bacterium Deinococccus radiodurans, so as to find the commonalities existing in their strategies of resistance on the one hand, and also the rationale behind the difference in D10, on the other. Genomic analysis of VITHBRA001 and VITHBRA024 has further helped us ascertain the difference in capability of radiation resistance between the two strains. Significantly, the genes such as uvsE (NER), frnE (protein protection), ppk1 and ppx (non-enzymatic metabolite production) and those for carotenoid biosynthesis, are endogenous to VITHBRA001, but absent in VITHBRA024, which could explain the former’s better radiation resistance. Further, this is the first-time study performed on any bacterial population inhabiting an HBRA. This study also brings forward the two species whose radiation resistance has not been reported thus far, and add to the knowledge on radiation resistant capabilities of the phylum Firmicutes which are abundantly observed in extreme environment.

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The ADP-ribose hydrolase NUDT5 is important for DNA repair

Cited by 11 publications

References 47 publications

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells

The novel phosphatase NUDT5 is a critical regulator of triple-negative breast cancer growth

Unraveling radiation resistance strategies in two bacterial strains from the high background radiation area of Chavara-Neendakara: A comprehensive whole genome analysis

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