Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Role of NFBD1 in global gene expression

ABSTRACT: NFBD1 (nuclear factor with BRCT domains 1), also known as MDC1 (mediator of DNA damage signaling 1), is a protein involved in the ATM signaling pathway in response to DNA damage. In addition to a role in signaling, NFBD1 possesses transactivation activity, suggesting that it may influence transcription. Furthermore, NFBD1 affects p53-mediated transcription in the presence of the DNA damaging agent adriamycin. Our goal was to determine if NFBD1 affects global gene expression with or without ionizing radiation-induced DNA damage. Moreover, we sought to separate p53-dependent from p53-independent events. Illumina microarray analysis was carried out on RNA extracted from cells treated with and without NFBD1 shRNA and/or p53 shRNA in the presence and absence of DNA damage. Surprisingly, we found that the expression of NFBD1-regulated genes was changed in both the presence and absence of DNA damage. Furthermore, most NFBD1-regulated genes were regulated independently of p53. The identification of NFBD1-regulated genes was confirmed with a second NFBD1-directed shRNA sequence. The role of NFBD1 in global gene expression both in the presence and absence of ionizing radiation was determined. p53-dependent and p53-dependent events regulated by NFBD1 depletion were studied. U2OS cells were treated with control, NFBD1 shRNA, and/or p53 shRNA-expressing retrovirus. Cells were then treated with ionizing radiation and total RNA was isolated for Illumina microarray analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Vince Schulz

PROVIDER: E-GEOD-23010 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

NFBD1/MDC1 regulates Cav1 and Cav2 independently of DNA damage and p53.

Wilson Kathleen A KA Colavito Sierra A SA Schulz Vincent V Wakefield Patricia Heffernan PH Sessa William W Tuck David D Stern David F DF

Molecular cancer research : MCR 20110506 6

NFBD1/MDC1 is involved in DNA damage checkpoint signaling and DNA repair. NFBD1 binds to the chromatin component γH2AX at sites of DNA damage, causing amplification of ataxia telangiectasia-mutated gene (ATM) pathway signaling and recruitment of DNA repair factors. Residues 508-995 of NFBD1 possess transactivation activity, suggesting a possible role of NFBD1 in transcription. Furthermore, NFBD1 influences p53-mediated transcription in response to adriamycin. We sought to determine the role of N ...[more]

PMID: 21551225

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Project description:Barr2017 - Dynamics of p21 in hTert-RPE1 cells This deteministic model reveals that a bistable switch created by Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, prevents premature S-phase exit upon DNA damage This model is described in the article: DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression. Barr AR, Cooper S, Heldt FS, Butera F, Stoy H, Mansfeld J, Novák B, Bakal C. Nat Commun 2017 Mar; 8: 14728 Abstract: Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability. This model is hosted on BioModels Database and identified by: BIOMD0000000660. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Role of NFBD1 in global gene expression

Publications

NFBD1/MDC1 regulates Cav1 and Cav2 independently of DNA damage and p53.

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