BACH2: A marker of DNA damage and ageing

L. M. Uittenboogaard, C. Payan-Gomez, J. Pothof, W. van IJcken, P. G. Mastroberardino, I. van der Pluijm, J. H J Hoeijmakers, M. Tresini

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

DNA damage and ageing share expression changes involving alterations in many aspects of metabolism, suppression of growth and upregulation of defence and genome maintenance systems. "Omics" technologies have permitted large-scale parallel measurements covering global cellular constituents and aided the identification of specific response pathways that change during ageing and after DNA damage. We have set out to identify genes with highly conserved response patterns through meta-analysis of mRNA expression datasets collected during natural ageing and accelerated ageing caused by a Transcription-Coupled Nucleotide Excision Repair (TC-NER) defect in a diverse set of organs and tissues in mice, and from in vitro UV-induced DNA damage in a variety of murine cells. The identified set of genes that show similar expression patterns in response to organ ageing (accelerated and normal), and endogenously and exogenously induced DNA damage, consists of genes involved in anti-oxidant systems and includes the transcription factor Bach2 as one of the most consistent markers. BACH2 was originally identified as a partner of the small Maf proteins and antagonist of the NRF2 anti-oxidant defence pathway and has been implicated in B-cell differentiation and immune system homeostasis. Although BACH2 has never before been associated with UV-induced damage or ageing, it shows a strong downregulation in both conditions. We have characterized the dynamics of Bach2 expression in response to DNA damage and show that it is a highly sensitive responder to transcription-blocking DNA lesions. Gene expression profiling using Affymetrix microarray analysis after siRNA-mediated silencing of Bach2 identified cell cycle and transcription regulation as the most significantly altered processes consistent with a function as transcription factor affecting proliferation. © 2013 Elsevier B.V.
Original languageEnglish (US)
Pages (from-to)982-992
Number of pages11
JournalDNA Repair
DOIs
StatePublished - Nov 1 2013

Fingerprint

DNA Damage
Aging of materials
DNA
Transcription
Genes
Oxidants
Maf Transcription Factors
Transcription Factors
Cells
Gene Expression Profiling
Microarray Analysis
DNA Repair
Immune system
Small Interfering RNA
Meta-Analysis
Microarrays
Cell Differentiation
Immune System
Cell Cycle
Metabolism

Cite this

Uittenboogaard, L. M., Payan-Gomez, C., Pothof, J., van IJcken, W., Mastroberardino, P. G., van der Pluijm, I., ... Tresini, M. (2013). BACH2: A marker of DNA damage and ageing. DNA Repair, 982-992. https://doi.org/10.1016/j.dnarep.2013.08.016
Uittenboogaard, L. M. ; Payan-Gomez, C. ; Pothof, J. ; van IJcken, W. ; Mastroberardino, P. G. ; van der Pluijm, I. ; Hoeijmakers, J. H J ; Tresini, M. / BACH2: A marker of DNA damage and ageing. In: DNA Repair. 2013 ; pp. 982-992.
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Uittenboogaard, LM, Payan-Gomez, C, Pothof, J, van IJcken, W, Mastroberardino, PG, van der Pluijm, I, Hoeijmakers, JHJ & Tresini, M 2013, 'BACH2: A marker of DNA damage and ageing', DNA Repair, pp. 982-992. https://doi.org/10.1016/j.dnarep.2013.08.016

BACH2: A marker of DNA damage and ageing. / Uittenboogaard, L. M.; Payan-Gomez, C.; Pothof, J.; van IJcken, W.; Mastroberardino, P. G.; van der Pluijm, I.; Hoeijmakers, J. H J; Tresini, M.

In: DNA Repair, 01.11.2013, p. 982-992.

Research output: Contribution to journalArticle

TY - JOUR

T1 - BACH2: A marker of DNA damage and ageing

AU - Uittenboogaard, L. M.

AU - Payan-Gomez, C.

AU - Pothof, J.

AU - van IJcken, W.

AU - Mastroberardino, P. G.

AU - van der Pluijm, I.

AU - Hoeijmakers, J. H J

AU - Tresini, M.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - DNA damage and ageing share expression changes involving alterations in many aspects of metabolism, suppression of growth and upregulation of defence and genome maintenance systems. "Omics" technologies have permitted large-scale parallel measurements covering global cellular constituents and aided the identification of specific response pathways that change during ageing and after DNA damage. We have set out to identify genes with highly conserved response patterns through meta-analysis of mRNA expression datasets collected during natural ageing and accelerated ageing caused by a Transcription-Coupled Nucleotide Excision Repair (TC-NER) defect in a diverse set of organs and tissues in mice, and from in vitro UV-induced DNA damage in a variety of murine cells. The identified set of genes that show similar expression patterns in response to organ ageing (accelerated and normal), and endogenously and exogenously induced DNA damage, consists of genes involved in anti-oxidant systems and includes the transcription factor Bach2 as one of the most consistent markers. BACH2 was originally identified as a partner of the small Maf proteins and antagonist of the NRF2 anti-oxidant defence pathway and has been implicated in B-cell differentiation and immune system homeostasis. Although BACH2 has never before been associated with UV-induced damage or ageing, it shows a strong downregulation in both conditions. We have characterized the dynamics of Bach2 expression in response to DNA damage and show that it is a highly sensitive responder to transcription-blocking DNA lesions. Gene expression profiling using Affymetrix microarray analysis after siRNA-mediated silencing of Bach2 identified cell cycle and transcription regulation as the most significantly altered processes consistent with a function as transcription factor affecting proliferation. © 2013 Elsevier B.V.

AB - DNA damage and ageing share expression changes involving alterations in many aspects of metabolism, suppression of growth and upregulation of defence and genome maintenance systems. "Omics" technologies have permitted large-scale parallel measurements covering global cellular constituents and aided the identification of specific response pathways that change during ageing and after DNA damage. We have set out to identify genes with highly conserved response patterns through meta-analysis of mRNA expression datasets collected during natural ageing and accelerated ageing caused by a Transcription-Coupled Nucleotide Excision Repair (TC-NER) defect in a diverse set of organs and tissues in mice, and from in vitro UV-induced DNA damage in a variety of murine cells. The identified set of genes that show similar expression patterns in response to organ ageing (accelerated and normal), and endogenously and exogenously induced DNA damage, consists of genes involved in anti-oxidant systems and includes the transcription factor Bach2 as one of the most consistent markers. BACH2 was originally identified as a partner of the small Maf proteins and antagonist of the NRF2 anti-oxidant defence pathway and has been implicated in B-cell differentiation and immune system homeostasis. Although BACH2 has never before been associated with UV-induced damage or ageing, it shows a strong downregulation in both conditions. We have characterized the dynamics of Bach2 expression in response to DNA damage and show that it is a highly sensitive responder to transcription-blocking DNA lesions. Gene expression profiling using Affymetrix microarray analysis after siRNA-mediated silencing of Bach2 identified cell cycle and transcription regulation as the most significantly altered processes consistent with a function as transcription factor affecting proliferation. © 2013 Elsevier B.V.

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DO - 10.1016/j.dnarep.2013.08.016

M3 - Article

SP - 982

EP - 992

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

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Uittenboogaard LM, Payan-Gomez C, Pothof J, van IJcken W, Mastroberardino PG, van der Pluijm I et al. BACH2: A marker of DNA damage and ageing. DNA Repair. 2013 Nov 1;982-992. https://doi.org/10.1016/j.dnarep.2013.08.016