Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks

GA Garinis; J.D. Mitchell; MJ Moorhouse; K Hanada; H de Waard; D Vandeputte; J Jans; K Brand; M Smid; PJ van der Spek; JHA Hoeijmakers; R Kanaar; GTJ van der Horst

doi:10.1038/sj.emboj.7600849

Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks

GA Garinis, J.D. Mitchell, MJ Moorhouse, K Hanada, H de Waard, D Vandeputte, J Jans, K Brand, M Smid, PJ van der Spek, JHA Hoeijmakers, R Kanaar, GTJ van der Horst^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Photolyase transgenic mice have opened new avenues to improve our understanding of the cytotoxic effects of ultraviolet (UV) light on skin by providing a means to selectively remove either cyclobutane pyrimidine dimers (CPDs) or pyrimidine (6-4) pyrimidone photoproducts. Here, we have taken a genomics approach to delineate pathways through which CPDs might contribute to the harmful effects of UV exposure. We show that CPDs, rather than other DNA lesions or damaged macromolecules, comprise the principal mediator of the cellular transcriptional response to UV. The most prominent pathway induced by CPDs is that associated with DNA double-strand break (DSB) signalling and repair. Moreover, we show that CPDs provoke accumulation of gamma-H2AX, P53bp1 and Rad51 foci as well as an increase in the amount of DSBs, which coincides with accumulation of cells in S phase. Thus, conversion of unrepaired CPD lesions into DNA breaks during DNA replication may comprise one of the principal instigators of UV-mediated cytotoxicity.

Original language	English
Pages (from-to)	3952-3962
Number of pages	11
Journal	EMBO Journal
Volume	24
Issue number	22
DOIs	https://doi.org/10.1038/sj.emboj.7600849
Publication status	Published - 16 Nov 2005

Keywords

DNA damage
functional genomics
photolyase
UV irradiation
DOUBLE-STRAND BREAKS
STALLED-REPLICATION FORKS
RIBOTOXIC STRESS-RESPONSE
HUMAN-CELLS
ATAXIA-TELANGIECTASIA
SIGNALING PATHWAYS
MAMMALIAN-CELLS
DAMAGE
REPAIR
GENE

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Garinis, GA., Mitchell, J. D., Moorhouse, MJ., Hanada, K., de Waard, H., Vandeputte, D., Jans, J., Brand, K., Smid, M., van der Spek, PJ., Hoeijmakers, JHA., Kanaar, R., & van der Horst, GTJ. (2005). Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks. EMBO Journal, 24(22), 3952-3962. https://doi.org/10.1038/sj.emboj.7600849

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title = "Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks",

abstract = "Photolyase transgenic mice have opened new avenues to improve our understanding of the cytotoxic effects of ultraviolet (UV) light on skin by providing a means to selectively remove either cyclobutane pyrimidine dimers (CPDs) or pyrimidine (6-4) pyrimidone photoproducts. Here, we have taken a genomics approach to delineate pathways through which CPDs might contribute to the harmful effects of UV exposure. We show that CPDs, rather than other DNA lesions or damaged macromolecules, comprise the principal mediator of the cellular transcriptional response to UV. The most prominent pathway induced by CPDs is that associated with DNA double-strand break (DSB) signalling and repair. Moreover, we show that CPDs provoke accumulation of gamma-H2AX, P53bp1 and Rad51 foci as well as an increase in the amount of DSBs, which coincides with accumulation of cells in S phase. Thus, conversion of unrepaired CPD lesions into DNA breaks during DNA replication may comprise one of the principal instigators of UV-mediated cytotoxicity.",

keywords = "DNA damage, functional genomics, photolyase, UV irradiation, DOUBLE-STRAND BREAKS, STALLED-REPLICATION FORKS, RIBOTOXIC STRESS-RESPONSE, HUMAN-CELLS, ATAXIA-TELANGIECTASIA, SIGNALING PATHWAYS, MAMMALIAN-CELLS, DAMAGE, REPAIR, GENE",

author = "GA Garinis and J.D. Mitchell and MJ Moorhouse and K Hanada and {de Waard}, H and D Vandeputte and J Jans and K Brand and M Smid and {van der Spek}, PJ and JHA Hoeijmakers and R Kanaar and {van der Horst}, GTJ",

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doi = "10.1038/sj.emboj.7600849",

language = "English",

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Garinis, GA, Mitchell, JD, Moorhouse, MJ, Hanada, K, de Waard, H, Vandeputte, D, Jans, J, Brand, K, Smid, M, van der Spek, PJ, Hoeijmakers, JHA, Kanaar, R & van der Horst, GTJ 2005, 'Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks', EMBO Journal, vol. 24, no. 22, pp. 3952-3962. https://doi.org/10.1038/sj.emboj.7600849

TY - JOUR

T1 - Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks

AU - Garinis, GA

AU - Mitchell, J.D.

AU - Moorhouse, MJ

AU - Hanada, K

AU - de Waard, H

AU - Vandeputte, D

AU - Jans, J

AU - Brand, K

AU - Smid, M

AU - van der Spek, PJ

AU - Hoeijmakers, JHA

AU - Kanaar, R

AU - van der Horst, GTJ

PY - 2005/11/16

Y1 - 2005/11/16

N2 - Photolyase transgenic mice have opened new avenues to improve our understanding of the cytotoxic effects of ultraviolet (UV) light on skin by providing a means to selectively remove either cyclobutane pyrimidine dimers (CPDs) or pyrimidine (6-4) pyrimidone photoproducts. Here, we have taken a genomics approach to delineate pathways through which CPDs might contribute to the harmful effects of UV exposure. We show that CPDs, rather than other DNA lesions or damaged macromolecules, comprise the principal mediator of the cellular transcriptional response to UV. The most prominent pathway induced by CPDs is that associated with DNA double-strand break (DSB) signalling and repair. Moreover, we show that CPDs provoke accumulation of gamma-H2AX, P53bp1 and Rad51 foci as well as an increase in the amount of DSBs, which coincides with accumulation of cells in S phase. Thus, conversion of unrepaired CPD lesions into DNA breaks during DNA replication may comprise one of the principal instigators of UV-mediated cytotoxicity.

AB - Photolyase transgenic mice have opened new avenues to improve our understanding of the cytotoxic effects of ultraviolet (UV) light on skin by providing a means to selectively remove either cyclobutane pyrimidine dimers (CPDs) or pyrimidine (6-4) pyrimidone photoproducts. Here, we have taken a genomics approach to delineate pathways through which CPDs might contribute to the harmful effects of UV exposure. We show that CPDs, rather than other DNA lesions or damaged macromolecules, comprise the principal mediator of the cellular transcriptional response to UV. The most prominent pathway induced by CPDs is that associated with DNA double-strand break (DSB) signalling and repair. Moreover, we show that CPDs provoke accumulation of gamma-H2AX, P53bp1 and Rad51 foci as well as an increase in the amount of DSBs, which coincides with accumulation of cells in S phase. Thus, conversion of unrepaired CPD lesions into DNA breaks during DNA replication may comprise one of the principal instigators of UV-mediated cytotoxicity.

KW - DNA damage

KW - functional genomics

KW - photolyase

KW - UV irradiation

KW - DOUBLE-STRAND BREAKS

KW - STALLED-REPLICATION FORKS

KW - RIBOTOXIC STRESS-RESPONSE

KW - HUMAN-CELLS

KW - ATAXIA-TELANGIECTASIA

KW - SIGNALING PATHWAYS

KW - MAMMALIAN-CELLS

KW - DAMAGE

KW - REPAIR

KW - GENE

U2 - 10.1038/sj.emboj.7600849

DO - 10.1038/sj.emboj.7600849

M3 - Article

SN - 0261-4189

VL - 24

SP - 3952

EP - 3962

JO - EMBO Journal

JF - EMBO Journal

IS - 22

ER -

Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks

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Keywords

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