Functional interplay between Parp-1 and SirT1 in genome integrity and chromatin-based processes

Rosy El Ramy; Najat Magroun; Nadia Messadecq; Laurent R. Gauthier; François D. Boussin; Ullas Kolthur-Seetharam; Valérie Schreiber; Michael W. McBurney; Paolo Sassone-Corsi; Françoise Dantzer

doi:10.1007/s00018-009-0105-4

The Effect ofPoly(ADP-ribose) Polymerase-1Gene 3′Untranslated Region Polymorphism in Colorectal Cancer Risk among Saudi Cohort

Disease Markers ◽

10.1155/2016/8289293 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Abdullah M. Alhadheq ◽

Jilani Purusottapatnam Shaik ◽

Abdullah Alamri ◽

Abdulrahman M. Aljebreen ◽

Othman Alharbi ◽

...

Keyword(s):

Colorectal Cancer ◽

Untranslated Region ◽

Excision Repair ◽

Tumor Location ◽

Genome Integrity ◽

Younger Age ◽

Colon And Rectum ◽

Spss Software ◽

Base Excision ◽

Parp 1

Background. DNA repair systems are essential for each cell to repair and maintain the genome integrity. Base excision repair pathway is one of the crucial pathways to maintain genome integrity andPARP-1plays a key role in BER pathway. The purpose of this study is to evaluate the association between polymorphisms inPARP-13′untranslated region (3′UTR) SNP rs8679 and its expression in colorectal cancer.Methods. Genotyping and gene expression were performed using TaqMan assays. The effects of age, gender, and tumor location were evaluated in cases and controls regarding the genotyping results. Resulting data was analyzed using SPSS software.Results and Conclusions. Genotyping analysis for SNP rs8679 showed decreased susceptibility to colorectal cancer at heterozygous TC allele and at minor allele C. Further this protective association was also observed in younger age patients (≤57), in female patients, and also in patients with tumors located at colon and rectum.PARP-1expression levels are significantly different in colorectal cancer compared to matched normal tissue. Our findings proved that the upregulation ofPARP-1is associated with tumor progression and poor prognosis in Saudi patients with colorectal cancer, suggesting thatPARP-1can be novel and valuable signatures for predicting the clinical outcome of patients with colorectal cancer.

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Targeting DNA Damage Response in Prostate and Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21218273 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8273

Author(s):

Antje M. Wengner ◽

Arne Scholz ◽

Bernard Haendler

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Dna Damage Response ◽

Large Scale ◽

Hormone Receptors ◽

Steroid Hormone ◽

Steroid Hormone Receptors ◽

Genome Integrity ◽

Damage Response ◽

Parp 1

Steroid hormone signaling induces vast gene expression programs which necessitate the local formation of transcription factories at regulatory regions and large-scale alterations of the genome architecture to allow communication among distantly related cis-acting regions. This involves major stress at the genomic DNA level. Transcriptionally active regions are generally instable and prone to breakage due to the torsional stress and local depletion of nucleosomes that make DNA more accessible to damaging agents. A dedicated DNA damage response (DDR) is therefore essential to maintain genome integrity at these exposed regions. The DDR is a complex network involving DNA damage sensor proteins, such as the poly(ADP-ribose) polymerase 1 (PARP-1), the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), the ataxia–telangiectasia-mutated (ATM) kinase and the ATM and Rad3-related (ATR) kinase, as central regulators. The tight interplay between the DDR and steroid hormone receptors has been unraveled recently. Several DNA repair factors interact with the androgen and estrogen receptors and support their transcriptional functions. Conversely, both receptors directly control the expression of agents involved in the DDR. Impaired DDR is also exploited by tumors to acquire advantageous mutations. Cancer cells often harbor germline or somatic alterations in DDR genes, and their association with disease outcome and treatment response led to intensive efforts towards identifying selective inhibitors targeting the major players in this process. The PARP-1 inhibitors are now approved for ovarian, breast, and prostate cancer with specific genomic alterations. Additional DDR-targeting agents are being evaluated in clinical studies either as single agents or in combination with treatments eliciting DNA damage (e.g., radiation therapy, including targeted radiotherapy, and chemotherapy) or addressing targets involved in maintenance of genome integrity. Recent preclinical and clinical findings made in addressing DNA repair dysfunction in hormone-dependent and -independent prostate and breast tumors are presented. Importantly, the combination of anti-hormonal therapy with DDR inhibition or with radiation has the potential to enhance efficacy but still needs further investigation.

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LDOC-1 and PARP-1 mRNA expression in leukocytes of father and son with cutaneous malignant melanoma

Open Medicine ◽

10.2478/s11536-012-0121-x ◽

2013 ◽

Vol 8 (2) ◽

pp. 204-207

Author(s):

Michele Salemi ◽

Pier Soma ◽

Rosita Condorelli ◽

Domenico Recupero ◽

Aldo Calogero

Keyword(s):

Malignant Melanoma ◽

Leucine Zipper ◽

Cutaneous Malignant Melanoma ◽

Genome Integrity ◽

Histological Evaluation ◽

Blood Leukocytes ◽

Low Levels ◽

Apoptosis Inducing Factor ◽

Parp 1 ◽

Father And Son

AbstractApoptosis is central to the biology of cutaneous malignant melanoma (CMM). The leucine zipper, down regulated in cancer 1 (LDOC-1) gene, is known to be a regulator of the nuclear factor kappa B (NF-kB) through inhibition of the same NF-kB. The poly (ADP-ribose) polymerase-1 (PARP1) gene plays an important role for the efficient maintenance of genome integrity. PARP-1 protein is required for the apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. We report here two interesting cases of family melanoma, a father and son 84 and 40 years old, respectively. The histological evaluation of the lesions of both men revealed diffused superficial melanoma with epithelioid cells. We evaluated the differential expression of LDOC-1 and PARP-1 mRNA in peripheral blood leukocytes of both the father and son. We found that both LDOC-1 and PARP-1 genes were down-regulated in both patients compared with those of controls. These data suggest that low levels of expression of LDOC-1 and PARP-1 mRNA may be associated with familial melanoma.

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Zinc finger protein E4F1 cooperates with PARP-1 and BRG1 to promote DNA double-strand break repair

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2019408118 ◽

2021 ◽

Vol 118 (11) ◽

pp. e2019408118

Author(s):

Céline Moison ◽

Jalila Chagraoui ◽

Marie-Christine Caron ◽

Jean-Philippe Gagné ◽

Yan Coulombe ◽

...

Keyword(s):

Dna Repair ◽

Zinc Finger ◽

Zinc Finger Protein ◽

Strand Break ◽

Dna Lesions ◽

Genome Integrity ◽

Dependent Manner ◽

Breast Cancers ◽

Dna Breaks ◽

Parp 1

Zinc finger (ZnF) proteins represent one of the largest families of human proteins, although most remain uncharacterized. Given that numerous ZnF proteins are able to interact with DNA and poly(ADP ribose), there is growing interest in understanding their mechanism of action in the maintenance of genome integrity. We now report that the ZnF protein E4F transcription factor 1 (E4F1) is an actor in DNA repair. Indeed, E4F1 is rapidly recruited, in a poly(ADP ribose) polymerase (PARP)-dependent manner, to DNA breaks and promotes ATR/CHK1 signaling, DNA-end resection, and subsequent homologous recombination. Moreover, we identify E4F1 as a regulator of the ATP-dependent chromatin remodeling SWI/SNF complex in DNA repair. E4F1 binds to the catalytic subunit BRG1/SMARCA4 and together with PARP-1 mediates its recruitment to DNA lesions. We also report that a proportion of human breast cancers show amplification and overexpression of E4F1 or BRG1 that are mutually exclusive with BRCA1/2 alterations. Together, these results reveal a function of E4F1 in the DNA damage response that orchestrates proper signaling and repair of double-strand breaks and document a molecular mechanism for its essential role in maintaining genome integrity and cell survival.

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