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Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity

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Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity. / Puumalainen, Marjo-Riitta; Lessel, Davor; Rüthemann, Peter; Kaczmarek, Nina; Bachmann, Karin; Ramadan, Kristijan; Naegeli, Hanspeter.

In: NAT COMMUN, Vol. 5, 01.01.2014, p. 3695.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Puumalainen, M-R, Lessel, D, Rüthemann, P, Kaczmarek, N, Bachmann, K, Ramadan, K & Naegeli, H 2014, 'Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity', NAT COMMUN, vol. 5, pp. 3695. https://doi.org/10.1038/ncomms4695

APA

Puumalainen, M-R., Lessel, D., Rüthemann, P., Kaczmarek, N., Bachmann, K., Ramadan, K., & Naegeli, H. (2014). Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity. NAT COMMUN, 5, 3695. https://doi.org/10.1038/ncomms4695

Vancouver

Puumalainen M-R, Lessel D, Rüthemann P, Kaczmarek N, Bachmann K, Ramadan K et al. Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity. NAT COMMUN. 2014 Jan 1;5:3695. https://doi.org/10.1038/ncomms4695

Bibtex

@article{9acccba3c94046e6be515ed8f420421b,
title = "Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity",
abstract = "DNA damage recognition subunits such as DDB2 and XPC protect the human skin from ultraviolet (UV) light-induced genome instability and cancer, as demonstrated by the devastating inherited syndrome xeroderma pigmentosum. Here we show that the beneficial DNA repair response triggered by these two genome caretakers critically depends on a dynamic spatiotemporal regulation of their homeostasis. The prolonged retention of DDB2 and XPC in chromatin, because of a failure to readily remove both recognition subunits by the ubiquitin-dependent p97/VCP/Cdc48 segregase complex, leads to impaired DNA excision repair of UV lesions. Surprisingly, the ensuing chromosomal aberrations in p97-deficient cells are alleviated by a concomitant downregulation of DDB2 or XPC. Also, genome instability resulting from an excess of DDB2 persisting in UV-irradiated cells is prevented by concurrent p97 overexpression. Our findings demonstrate that DNA damage sensors and repair initiators acquire unexpected genotoxic properties if not controlled by timely extraction from chromatin.",
keywords = "Chromatin, Cloning, Molecular, Colony-Forming Units Assay, DNA Damage, DNA Primers, DNA Repair, DNA-Binding Proteins, Genomic Instability, HEK293 Cells, HeLa Cells, Humans, Immunoblotting, Microscopy, Fluorescence, RNA, Small Interfering, Ultraviolet Rays",
author = "Marjo-Riitta Puumalainen and Davor Lessel and Peter R{\"u}themann and Nina Kaczmarek and Karin Bachmann and Kristijan Ramadan and Hanspeter Naegeli",
year = "2014",
month = jan,
day = "1",
doi = "10.1038/ncomms4695",
language = "English",
volume = "5",
pages = "3695",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity

AU - Puumalainen, Marjo-Riitta

AU - Lessel, Davor

AU - Rüthemann, Peter

AU - Kaczmarek, Nina

AU - Bachmann, Karin

AU - Ramadan, Kristijan

AU - Naegeli, Hanspeter

PY - 2014/1/1

Y1 - 2014/1/1

N2 - DNA damage recognition subunits such as DDB2 and XPC protect the human skin from ultraviolet (UV) light-induced genome instability and cancer, as demonstrated by the devastating inherited syndrome xeroderma pigmentosum. Here we show that the beneficial DNA repair response triggered by these two genome caretakers critically depends on a dynamic spatiotemporal regulation of their homeostasis. The prolonged retention of DDB2 and XPC in chromatin, because of a failure to readily remove both recognition subunits by the ubiquitin-dependent p97/VCP/Cdc48 segregase complex, leads to impaired DNA excision repair of UV lesions. Surprisingly, the ensuing chromosomal aberrations in p97-deficient cells are alleviated by a concomitant downregulation of DDB2 or XPC. Also, genome instability resulting from an excess of DDB2 persisting in UV-irradiated cells is prevented by concurrent p97 overexpression. Our findings demonstrate that DNA damage sensors and repair initiators acquire unexpected genotoxic properties if not controlled by timely extraction from chromatin.

AB - DNA damage recognition subunits such as DDB2 and XPC protect the human skin from ultraviolet (UV) light-induced genome instability and cancer, as demonstrated by the devastating inherited syndrome xeroderma pigmentosum. Here we show that the beneficial DNA repair response triggered by these two genome caretakers critically depends on a dynamic spatiotemporal regulation of their homeostasis. The prolonged retention of DDB2 and XPC in chromatin, because of a failure to readily remove both recognition subunits by the ubiquitin-dependent p97/VCP/Cdc48 segregase complex, leads to impaired DNA excision repair of UV lesions. Surprisingly, the ensuing chromosomal aberrations in p97-deficient cells are alleviated by a concomitant downregulation of DDB2 or XPC. Also, genome instability resulting from an excess of DDB2 persisting in UV-irradiated cells is prevented by concurrent p97 overexpression. Our findings demonstrate that DNA damage sensors and repair initiators acquire unexpected genotoxic properties if not controlled by timely extraction from chromatin.

KW - Chromatin

KW - Cloning, Molecular

KW - Colony-Forming Units Assay

KW - DNA Damage

KW - DNA Primers

KW - DNA Repair

KW - DNA-Binding Proteins

KW - Genomic Instability

KW - HEK293 Cells

KW - HeLa Cells

KW - Humans

KW - Immunoblotting

KW - Microscopy, Fluorescence

KW - RNA, Small Interfering

KW - Ultraviolet Rays

U2 - 10.1038/ncomms4695

DO - 10.1038/ncomms4695

M3 - SCORING: Journal article

C2 - 24770583

VL - 5

SP - 3695

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -