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SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response.

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SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response. / Mund, Andreas; Schubert, Tobias; Staege, Hannah; Kinkley, Sarah; Reumann, Kerstin; Kriegs, Malte; Fritsch, Lauriane; Battisti, Valentine; Ait-Si-Ali, Slimane; Hoffbeck, Anne-Sophie; Soutoglou, Evi; Will, Hans.

In: NUCLEIC ACIDS RES, Vol. 40, No. 22, 22, 2012, p. 11363-11379.

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

Harvard

Mund, A, Schubert, T, Staege, H, Kinkley, S, Reumann, K, Kriegs, M, Fritsch, L, Battisti, V, Ait-Si-Ali, S, Hoffbeck, A-S, Soutoglou, E & Will, H 2012, 'SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response.', NUCLEIC ACIDS RES, vol. 40, no. 22, 22, pp. 11363-11379. https://doi.org/10.1093/nar/gks868

APA

Mund, A., Schubert, T., Staege, H., Kinkley, S., Reumann, K., Kriegs, M., Fritsch, L., Battisti, V., Ait-Si-Ali, S., Hoffbeck, A-S., Soutoglou, E., & Will, H. (2012). SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response. NUCLEIC ACIDS RES, 40(22), 11363-11379. [22]. https://doi.org/10.1093/nar/gks868

Vancouver

Mund A, Schubert T, Staege H, Kinkley S, Reumann K, Kriegs M et al. SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response. NUCLEIC ACIDS RES. 2012;40(22):11363-11379. 22. https://doi.org/10.1093/nar/gks868

Bibtex

@article{e431c6391a9a4d899cb588ba920f22ac,
title = "SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response.",
abstract = "Survival time-associated plant homeodomain (PHD) finger protein in Ovarian Cancer 1 (SPOC1, also known as PHF13) is known to modulate chromatin structure and is essential for testicular stem-cell differentiation. Here we show that SPOC1 is recruited to DNA double-strand breaks (DSBs) in an ATM-dependent manner. Moreover, SPOC1 localizes at endogenous repair foci, including OPT domains and accumulates at large DSB repair foci characteristic for delayed repair at heterochromatic sites. SPOC1 depletion enhances the kinetics of ionizing radiation-induced foci (IRIF) formation after ?-irradiation (?-IR), non-homologous end-joining (NHEJ) repair activity, and cellular radioresistance, but impairs homologous recombination (HR) repair. Conversely, SPOC1 overexpression delays IRIF formation and ?H2AX expansion, reduces NHEJ repair activity and enhances cellular radiosensitivity. SPOC1 mediates dose-dependent changes in chromatin association of DNA compaction factors KAP-1, HP1-? and H3K9 methyltransferases (KMT) GLP, G9A and SETDB1. In addition, SPOC1 interacts with KAP-1 and H3K9 KMTs, inhibits KAP-1 phosphorylation and enhances H3K9 trimethylation. These findings provide the first evidence for a function of SPOC1 in DNA damage response (DDR) and repair. SPOC1 acts as a modulator of repair kinetics and choice of pathways. This involves its dose-dependent effects on DNA damage sensors, repair mediators and key regulators of chromatin structure.",
keywords = "Humans, Cell Line, Repressor Proteins/metabolism, Transcription Factors/*metabolism, *DNA Repair, DNA-Binding Proteins/*metabolism, Chromatin/*metabolism, DNA Breaks, Double-Stranded, DNA End-Joining Repair, Gamma Rays, Heterochromatin, Histone-Lysine N-Methyltransferase/metabolism, Radiation Tolerance, Recombinational DNA Repair, Humans, Cell Line, Repressor Proteins/metabolism, Transcription Factors/*metabolism, *DNA Repair, DNA-Binding Proteins/*metabolism, Chromatin/*metabolism, DNA Breaks, Double-Stranded, DNA End-Joining Repair, Gamma Rays, Heterochromatin, Histone-Lysine N-Methyltransferase/metabolism, Radiation Tolerance, Recombinational DNA Repair",
author = "Andreas Mund and Tobias Schubert and Hannah Staege and Sarah Kinkley and Kerstin Reumann and Malte Kriegs and Lauriane Fritsch and Valentine Battisti and Slimane Ait-Si-Ali and Anne-Sophie Hoffbeck and Evi Soutoglou and Hans Will",
year = "2012",
doi = "10.1093/nar/gks868",
language = "English",
volume = "40",
pages = "11363--11379",
journal = "NUCLEIC ACIDS RES",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "22",

}

RIS

TY - JOUR

T1 - SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response.

AU - Mund, Andreas

AU - Schubert, Tobias

AU - Staege, Hannah

AU - Kinkley, Sarah

AU - Reumann, Kerstin

AU - Kriegs, Malte

AU - Fritsch, Lauriane

AU - Battisti, Valentine

AU - Ait-Si-Ali, Slimane

AU - Hoffbeck, Anne-Sophie

AU - Soutoglou, Evi

AU - Will, Hans

PY - 2012

Y1 - 2012

N2 - Survival time-associated plant homeodomain (PHD) finger protein in Ovarian Cancer 1 (SPOC1, also known as PHF13) is known to modulate chromatin structure and is essential for testicular stem-cell differentiation. Here we show that SPOC1 is recruited to DNA double-strand breaks (DSBs) in an ATM-dependent manner. Moreover, SPOC1 localizes at endogenous repair foci, including OPT domains and accumulates at large DSB repair foci characteristic for delayed repair at heterochromatic sites. SPOC1 depletion enhances the kinetics of ionizing radiation-induced foci (IRIF) formation after ?-irradiation (?-IR), non-homologous end-joining (NHEJ) repair activity, and cellular radioresistance, but impairs homologous recombination (HR) repair. Conversely, SPOC1 overexpression delays IRIF formation and ?H2AX expansion, reduces NHEJ repair activity and enhances cellular radiosensitivity. SPOC1 mediates dose-dependent changes in chromatin association of DNA compaction factors KAP-1, HP1-? and H3K9 methyltransferases (KMT) GLP, G9A and SETDB1. In addition, SPOC1 interacts with KAP-1 and H3K9 KMTs, inhibits KAP-1 phosphorylation and enhances H3K9 trimethylation. These findings provide the first evidence for a function of SPOC1 in DNA damage response (DDR) and repair. SPOC1 acts as a modulator of repair kinetics and choice of pathways. This involves its dose-dependent effects on DNA damage sensors, repair mediators and key regulators of chromatin structure.

AB - Survival time-associated plant homeodomain (PHD) finger protein in Ovarian Cancer 1 (SPOC1, also known as PHF13) is known to modulate chromatin structure and is essential for testicular stem-cell differentiation. Here we show that SPOC1 is recruited to DNA double-strand breaks (DSBs) in an ATM-dependent manner. Moreover, SPOC1 localizes at endogenous repair foci, including OPT domains and accumulates at large DSB repair foci characteristic for delayed repair at heterochromatic sites. SPOC1 depletion enhances the kinetics of ionizing radiation-induced foci (IRIF) formation after ?-irradiation (?-IR), non-homologous end-joining (NHEJ) repair activity, and cellular radioresistance, but impairs homologous recombination (HR) repair. Conversely, SPOC1 overexpression delays IRIF formation and ?H2AX expansion, reduces NHEJ repair activity and enhances cellular radiosensitivity. SPOC1 mediates dose-dependent changes in chromatin association of DNA compaction factors KAP-1, HP1-? and H3K9 methyltransferases (KMT) GLP, G9A and SETDB1. In addition, SPOC1 interacts with KAP-1 and H3K9 KMTs, inhibits KAP-1 phosphorylation and enhances H3K9 trimethylation. These findings provide the first evidence for a function of SPOC1 in DNA damage response (DDR) and repair. SPOC1 acts as a modulator of repair kinetics and choice of pathways. This involves its dose-dependent effects on DNA damage sensors, repair mediators and key regulators of chromatin structure.

KW - Humans

KW - Cell Line

KW - Repressor Proteins/metabolism

KW - Transcription Factors/metabolism

KW - DNA Repair

KW - DNA-Binding Proteins/metabolism

KW - Chromatin/metabolism

KW - DNA Breaks, Double-Stranded

KW - DNA End-Joining Repair

KW - Gamma Rays

KW - Heterochromatin

KW - Histone-Lysine N-Methyltransferase/metabolism

KW - Radiation Tolerance

KW - Recombinational DNA Repair

KW - Humans

KW - Cell Line

KW - Repressor Proteins/metabolism

KW - Transcription Factors/metabolism

KW - DNA Repair

KW - DNA-Binding Proteins/metabolism

KW - Chromatin/metabolism

KW - DNA Breaks, Double-Stranded

KW - DNA End-Joining Repair

KW - Gamma Rays

KW - Heterochromatin

KW - Histone-Lysine N-Methyltransferase/metabolism

KW - Radiation Tolerance

KW - Recombinational DNA Repair

U2 - 10.1093/nar/gks868

DO - 10.1093/nar/gks868

M3 - SCORING: Journal article

VL - 40

SP - 11363

EP - 11379

JO - NUCLEIC ACIDS RES

JF - NUCLEIC ACIDS RES

SN - 0305-1048

IS - 22

M1 - 22

ER -