The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
The ATM Substrate KAP1 Controls DNA Repair in Heterochromatin: Regulation by HP1 Proteins and Serine 473/824 Phosphorylation
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Abstract
The repair of DNA damage in highly compact, transcriptionally silent heterochromatin requires that repair and chromatin packaging machineries be tightly coupled and regulated. KAP1 is a heterochromatin protein and co-repressor that binds to HP1 during gene silencing but is also robustly phosphorylated by Ataxia telangiectasia mutated (ATM) at serine 824 in response to DNA damage. The interplay between HP1-KAP1 binding/ATM phosphorylation during DNA repair is not known. We show that HP1α and unmodified KAP1 are enriched in endogenous heterochromatic loci and at a silent transgene prior to damage. Following damage, γH2AX and pKAP1-s824 rapidly increase and persist at these loci. Cells that lack HP1 fail to form discreet pKAP1-s824 foci after damage but levels are higher and more persistent. KAP1 is phosphorylated at serine 473 in response to DNA damage and its levels are also modulated by HP1. Unlike pKAP1-s824, pKAP1-s473 does not accumulate at damage foci but is diffusely localized in the nucleus. While HP1 association tempers KAP1 phosphorylation, this interaction also slows the resolution of γH2AX foci. Thus, HP1-dependent regulation of KAP1 influences DNA repair in heterochromatin. Mol Cancer Res; 10(3); 401–14. ©2011 AACR.
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“post-translational modification of KAP1 plays a critical role in determining which cellular context the protein will function in; for example sumoylated KAP1 promotes regulation of gene expression, while phosphorylated KAP1 promotes DNA repair41,42.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [42]
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“analysis of promoter arrays41,42 showed that SIRT6 only co-occupies approximately 10% of KAP1 bound promoters”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [42]
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Cites
Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins
Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., & Jenuwein, T. (2001) · Nature · doi:10.1038/35065132 · Cited by 2,868
Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo
Rogakou, E. P., Boon, C., Redon, C., & Bonner, W. M. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.5.905 · Cited by 2,422
ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks
Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., & Chen, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100466200 · Cited by 1,954
Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly
Nakayama, J.-I., Rice, J. C., Strahl, B. D., Allis, C. D., & Grewal, S. I. S. (2001) · Science · doi:10.1126/science.1060118 · Cited by 1,739
Schultz, D. C., Ayyanathan, K., Negorev, D., Maul, G. G., & Rauscher, F. J. (2002) · Genes & Development · doi:10.1101/gad.973302 · Cited by 1,313
Self-citationStucki, M., Clapperton, J. A., Mohammad, D. H., Yaffe, M. B., Smerdon, S. J., & Jackson, S. P. (2005) · Cell · doi:10.1016/j.cell.2005.09.038 · Cited by 1,164
Méndez, J., & Stillman, B. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8602-8612.2000 · Cited by 925
ATM Signaling Facilitates Repair of DNA Double-Strand Breaks Associated with Heterochromatin
Goodarzi, A. A., Noon, A. T., Deckbar, D., Ziv, Y., Shiloh, Y., Löbrich, M., & Jeggo, P. A. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.05.017 · Cited by 836
Ziv, Y., Bielopolski, D., Galanty, Y., Lukas, C., Taya, Y., Schultz, D. C., Lukas, J., Bekker-Jensen, S., Bartek, J., & Shiloh, Y. (2006) · Nature Cell Biology · doi:10.1038/ncb1446 · Cited by 735
From Silencing to Gene Expression
Janicki, S. M., Tsukamoto, T., Salghetti, S. E., Tansey, W. P., Sachidanandam, R., Prasanth, K. V., Ried, T., Shav-Tal, Y., Bertrand, E., Singer, R. H., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00171-0 · Cited by 704
Self-citationKAP-1, a novel corepressor for the highly conserved KRAB repression domain.Preprint
Friedman, J. R., Fredericks, W. J., Jensen, D. E., Speicher, D. W., Huang, X., Neilson, E. G., & Rauscher, F. J. (1996) · Genes & Development · doi:10.1101/gad.10.16.2067 · Cited by 692
Self-citationSchultz, D., Friedman, J. R., & Rauscher, F. J. (2001) · Genes & Development · doi:10.1101/gad.869501 · Cited by 530
Self-citationPositional stability of single double-strand breaks in mammalian cells
Soutoglou, E., Dorn, J. F., Sengupta, K., Jasin, M., Nussenzweig, A., Ried, T., Danuser, G., & Misteli, T. (2007) · Nature Cell Biology · doi:10.1038/ncb1591 · Cited by 509
Ivanov, A. V., Peng, H., Yurchenko, V., Yap, K. L., Negorev, D. G., Schultz, D. C., Psulkowski, E., Fredericks, W. J., White, D. E., Maul, G. G., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.11.012 · Cited by 432
Self-citationMdc1 couples DNA double‐strand break recognition by Nbs1 with its H2AX‐dependent chromatin retention
Lukas, C., Melander, F., Stucki, M., Falck, J., Bekker‐Jensen, S., Goldberg, M., Lerenthal, Y., Jackson, S. P., Bártek, J., & Lukas, J. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600269 · Cited by 399
Ryan, R. F., Schultz, D., Ayyanathan, K., Singh, P. B., Friedman, J. R., Fredericks, W. J., & Rauscher, F. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4366 · Cited by 382
Self-citationNielsen, A. L., Ortiz, J. A., You, J., Oulad‐Abdelghani, M., Khechumian, R., Gansmuller, A., Chambon, P., & Losson, R. (1999) · The EMBO Journal · doi:10.1093/emboj/18.22.6385 · Cited by 361
Ayyanathan, K., Lechner, M. S., Bell, P., Maul, G. G., Schultz, D., Yamada, Y., Tanaka, K., Torigoe, K., & Rauscher, F. J. (2003) · Genes & Development · doi:10.1101/gad.1102803 · Cited by 356
Self-citationNoon, A. T., Shibata, A., Rief, N., Löbrich, M., Stewart, G. S., Jeggo, P. A., & Goodarzi, A. A. (2010) · Nature Cell Biology · doi:10.1038/ncb2017 · Cited by 339
Sripathy, S. P., Stevens, J., & Schultz, D. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00487-06 · Cited by 323 · cited 2×
“KAP1-Mut2 does not colocalize with HP1 at pericentric heterochromatin and shows reduced transcriptional repressor activity (18).”
Localization and phosphorylation of HP1 proteins during the cell cycle in mammalian cells
Minc, E., Allory, Y., Worman, H. J., Courvalin, J., & Buendia, B. (1999) · Chromosoma · doi:10.1007/s004120050372 · Cited by 322
ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses
Yang, H. J. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg137 · Cited by 290
Zhou, B. S., Chaturvedi, P., Spring, K. J., Scott, S. P., Johanson, R. A., Mishra, R., Mattern, M. R., Winkler, J. D., & Khanna, K. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10342 · Cited by 278
Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
Kim, J., Kruhlak, M. J., Dotiwala, F., Nussenzweig, A., & Haber, J. E. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200612031 · Cited by 276
Heterochromatin and RNAi Are Required to Establish CENP-A Chromatin at Centromeres
Folco, H. D., Pidoux, A. L., Urano, T., & Allshire, R. C. (2008) · Science · doi:10.1126/science.1150944 · Cited by 275
Lechner, M. S., Begg, G. E., Speicher, D. W., & Rauscher, F. J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.17.6449-6465.2000 · Cited by 210
Self-citationCallén, E., Janković, M., Wong, N., Zha, S., Chen, H.-T., Difilippantonio, S., Virgilio, M. D., Heidkamp, G. F., Alt, F. W., Nussenzweig, A., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.04.025 · Cited by 205
HP1γ associates with euchromatin and heterochromatin in mammalian nuclei and chromosomes
Minc, E., Courvalin, J., & Buendia, B. (2000) · Cytogenetic and Genome Research · doi:10.1159/000056789 · Cited by 171
White, D. E., Negorev, D. G., Peng, H., Ivanov, A. V., Maul, G. G., & Rauscher, F. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-4138 · Cited by 147
Self-citationH2AX chromatin structures and their response to DNA damage revealed by 4Pi microscopy
Bewersdorf, J., Bennett, B. T., & Knight, K. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608709103 · Cited by 125
Heterochromatin Protein 1 Is Involved in Control of Telomere Elongation in Drosophila melanogaster
Savitsky, M., Кравчук, О. И., Melnikova, L. S., & Georgiev, P. G. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.9.3204-3218.2002 · Cited by 113
Cammas, F. M., Herzog, M., Lerouge, T., Chambon, P., & Losson, R. (2004) · Genes & Development · doi:10.1101/gad.302904 · Cited by 107
Cammas, F. M., Oulad‐Abdelghani, M., Vonesch, J., Huss-Garcia, Y., Chambon, P., & Losson, R. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.17.3439 · Cited by 96
Mahrhofer, H., Bürger, S., Oppitz, U., Flentje, M. P., & Djuzenova, C. S. (2006) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2005.09.037 · Cited by 78
Chang, C., Chou, H.-Y. E., Lin, Y.-S., Huang, K.-H., Chang, C.-J., Hsu, T.-C., & Lee, S.-C. (2008) · BMC Molecular Biology · doi:10.1186/1471-2199-9-61 · Cited by 64
Self-citationImmunoprecipitation techniques for the analysis of transcription factor complexes
Klenova, E. M. (2002) · Methods · doi:10.1016/s1046-2023(02)00029-4 · Cited by 54
Kiyomitsu, T., Iwasaki, O., Obuse, C., & Yanagida, M. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200908096 · Cited by 50
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Van Meter, M., Kashyap, M., Rezazadeh, S., Geneva, A. J., Morello, T. D., Seluanov, A., & Gorbunova, V. (2014) · Nature Communications · doi:10.1038/ncomms6011 · Cited by 456
“Finally, it is worth noting that post-translational modification of KAP1 plays a critical role in determining which cellular context the protein will function in; for example sumoylated KAP1 promotes regulation of gene expression, while phosphorylated KAP1 promotes DNA repair 41,42 .”
The same, only different – DNA damage checkpoints and their reversal throughout the cell cycle
Shaltiël, I. A., Krenning, L., Bruinsma, W., & Medema, R. H. (2015) · Journal of Cell Science · doi:10.1242/jcs.163766 · Cited by 310
The complexity of TRIM28 contribution to cancer
Czerwińska, P., Mazurek, S., & Wiznerowicz, M. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0374-4 · Cited by 285
TRIM28 regulates RNA polymerase II promoter-proximal pausing and pause release
Bunch, H., Zheng, X., Burkholder, A., Dillon, S. T., Motola, S., Birrane, G., Ebmeier, C. C., Levine, S. S., Fargo, D. C., Hu, G., et al. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2878 · Cited by 143
Interplay between Epigenetics and Genetics in Cancer
Choi, J. D., & Lee, J.-S. (2013) · Genomics & Informatics · doi:10.5808/gi.2013.11.4.164 · Cited by 131
Metadata
- Authors
- White, D., Rafalska-Metcalf, I. U., Ivanov, A. V., Corsinotti, A., Peng, H., Lee, S.-C., Trono, D., Janicki, S. M., & Rauscher, F. J.
- Affiliations
- The Wistar Institute (US)
- Corresponding author
- Rauscher, Frank J.
- Venue
- Molecular Cancer Research
- Published
- 2012-03-01
- Volume
- 10
- Issue
- 3
- Pages
- 401-414
- ISSN
- 1541-7786 (ISSN-L)
- 1557-3125
- PMC
- PMC4894472
- OpenAlex
- W2100197820
- Cited by
- 152
- References
- 37
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 15 · 2023: 9 · 2022: 7 · 2021: 14 · 2020: 9 · 2019: 8 · 2018: 8 · 2017: 12 · 2016: 11 · 2015: 14 · 2014: 13 · 2013: 4 · 2012: 3
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Cancer Institute (R01CA129833, CA010815, CA129833, CA126283, F32CA126283, P30CA010815)
- National Center for Research Resources (P20 RR16440, P20RR016440)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- KAP1, ATM, HP1, heterochromatin, DNA repair, γH2AX foci, gene silencing, chromatin condensation, DNA damage response
- MeSH terms
- Tripartite Motif-Containing Protein 28, Chromobox Protein Homolog 5, Amino Acid Sequence, Animals, Cell Fractionation, Chromosomal Proteins, Non-Histone, DNA Repair, DNA-Binding Proteins, Heterochromatin, Histones, Humans, Immunohistochemistry, Models, Biological, Molecular Sequence Data, Nuclear Proteins, Phosphorylation, Phosphoserine, Repressor Proteins, Substrate Specificity, Blotting, Western, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Transgenes, Tumor Suppressor Proteins, NIH 3T3 Cells, Mutant Proteins, Mice, Gene Knockdown Techniques, Ataxia Telangiectasia Mutated Proteins
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