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

George A. Garinis; James R. Mitchell; Michael J. Moorhouse; Katsuhiro Hanada; Harm De Waard; Dimitri Vandeputte; Judith Jans; Karl Brand; Marcel Smid; Peter J. Van Der Spek; Jan H.J. Hoeijmakers; Roland Kanaar; Gijsbertus T.J. Van Der Horst

doi:10.1038/sj.emboj.7600849

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

George A. Garinis, James R. Mitchell, Michael J. Moorhouse, Katsuhiro Hanada, Harm De Waard, Dimitri Vandeputte, Judith Jans, Karl Brand, Marcel Smid, Peter J. Van Der Spek, Jan H.J. Hoeijmakers, Roland Kanaar, Gijsbertus T.J. Van Der Horst

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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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 γ-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.

Originele taal-2	Engels
Pagina's (van-tot)	3952-3962
Aantal pagina's	11
Tijdschrift	EMBO Journal
Volume	24
Nummer van het tijdschrift	22
DOI's	https://doi.org/10.1038/sj.emboj.7600849
Status	Gepubliceerd - 16 nov. 2005
Extern gepubliceerd	Ja

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Garinis, G. A., Mitchell, J. R., Moorhouse, M. J., Hanada, K., De Waard, H., Vandeputte, D., Jans, J., Brand, K., Smid, M., Van Der Spek, P. J., Hoeijmakers, J. H. J., Kanaar, R., & Van Der Horst, G. T. J. (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

@article{4d1f97bdb8604f65a80cedc4f2e054a5,

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 γ-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",

author = "Garinis, {George A.} and Mitchell, {James R.} and Moorhouse, {Michael J.} and Katsuhiro Hanada and {De Waard}, Harm and Dimitri Vandeputte and Judith Jans and Karl Brand and Marcel Smid and {Van Der Spek}, {Peter J.} and Hoeijmakers, {Jan H.J.} and Roland Kanaar and {Van Der Horst}, {Gijsbertus T.J.}",

year = "2005",

month = nov,

day = "16",

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

language = "English",

volume = "24",

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journal = "EMBO Journal",

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}

Garinis, GA, Mitchell, JR, Moorhouse, MJ, Hanada, K, De Waard, H, Vandeputte, D, Jans, J, Brand, K, Smid, M, Van Der Spek, PJ, Hoeijmakers, JHJ, 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, nr. 22, blz. 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, George A.

AU - Mitchell, James R.

AU - Moorhouse, Michael J.

AU - Hanada, Katsuhiro

AU - De Waard, Harm

AU - Vandeputte, Dimitri

AU - Jans, Judith

AU - Brand, Karl

AU - Smid, Marcel

AU - Van Der Spek, Peter J.

AU - Hoeijmakers, Jan H.J.

AU - Kanaar, Roland

AU - Van Der Horst, Gijsbertus T.J.

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 γ-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 γ-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

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

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