Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks
DNA double-strand breaks (DSBs) elicit the so-called DNA damage response (DDR), largely relying on ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PKcs), two members of the PI3K-like kinase family, whose respective functions during the sequential steps of the DDR remains co...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471501178X |
| _version_ | 1819013343697960960 |
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| author | Pierre Caron Jonathan Choudjaye Thomas Clouaire Béatrix Bugler Virginie Daburon Marion Aguirrebengoa Thomas Mangeat Jason S. Iacovoni Alejandro Álvarez-Quilón Felipe Cortés-Ledesma Gaëlle Legube |
| author_facet | Pierre Caron Jonathan Choudjaye Thomas Clouaire Béatrix Bugler Virginie Daburon Marion Aguirrebengoa Thomas Mangeat Jason S. Iacovoni Alejandro Álvarez-Quilón Felipe Cortés-Ledesma Gaëlle Legube |
| author_sort | Pierre Caron |
| collection | DOAJ |
| description | DNA double-strand breaks (DSBs) elicit the so-called DNA damage response (DDR), largely relying on ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PKcs), two members of the PI3K-like kinase family, whose respective functions during the sequential steps of the DDR remains controversial. Using the DIvA system (DSB inducible via AsiSI) combined with high-resolution mapping and advanced microscopy, we uncovered that both ATM and DNA-PKcs spread in cis on a confined region surrounding DSBs, independently of the pathway used for repair. However, once recruited, these kinases exhibit non-overlapping functions on end joining and γH2AX domain establishment. More specifically, we found that ATM is required to ensure the association of multiple DSBs within “repair foci.” Our results suggest that ATM acts not only on chromatin marks but also on higher-order chromatin organization to ensure repair accuracy and survival. |
| first_indexed | 2024-12-21T01:58:27Z |
| format | Article |
| id | doaj.art-ade3514d2cc9404f8b5668e7ba76674c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T01:58:27Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ade3514d2cc9404f8b5668e7ba76674c2022-12-21T19:19:42ZengElsevierCell Reports2211-12472015-11-011381598160910.1016/j.celrep.2015.10.024Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand BreaksPierre Caron0Jonathan Choudjaye1Thomas Clouaire2Béatrix Bugler3Virginie Daburon4Marion Aguirrebengoa5Thomas Mangeat6Jason S. Iacovoni7Alejandro Álvarez-Quilón8Felipe Cortés-Ledesma9Gaëlle Legube10Université de Toulouse, UPS, LBCMCP, 118 route de Narbonne, 31062 Toulouse, FranceUniversité de Toulouse, UPS, LBCMCP, 118 route de Narbonne, 31062 Toulouse, FranceUniversité de Toulouse, UPS, LBCMCP, 118 route de Narbonne, 31062 Toulouse, FranceUniversité de Toulouse, UPS, LBCMCP, 118 route de Narbonne, 31062 Toulouse, FranceUniversité de Toulouse, UPS, LBCMCP, 118 route de Narbonne, 31062 Toulouse, FranceUniversité de Toulouse, UPS, LBCMCP, 118 route de Narbonne, 31062 Toulouse, FranceUniversité de Toulouse, UPS, LBCMCP, 118 route de Narbonne, 31062 Toulouse, FranceBioinformatic Plateau I2MC, INSERM and University of Toulouse, 1 Avenue Jean Poulhes, BP 84225, 31432 Toulouse Cedex 4, FranceCentro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), CSIC-Universidad de Sevilla, Sevilla 41092, SpainCentro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), CSIC-Universidad de Sevilla, Sevilla 41092, SpainUniversité de Toulouse, UPS, LBCMCP, 118 route de Narbonne, 31062 Toulouse, FranceDNA double-strand breaks (DSBs) elicit the so-called DNA damage response (DDR), largely relying on ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PKcs), two members of the PI3K-like kinase family, whose respective functions during the sequential steps of the DDR remains controversial. Using the DIvA system (DSB inducible via AsiSI) combined with high-resolution mapping and advanced microscopy, we uncovered that both ATM and DNA-PKcs spread in cis on a confined region surrounding DSBs, independently of the pathway used for repair. However, once recruited, these kinases exhibit non-overlapping functions on end joining and γH2AX domain establishment. More specifically, we found that ATM is required to ensure the association of multiple DSBs within “repair foci.” Our results suggest that ATM acts not only on chromatin marks but also on higher-order chromatin organization to ensure repair accuracy and survival.http://www.sciencedirect.com/science/article/pii/S221112471501178XDSB repairchromatinPI 3-kinasesγH2AXChIP-chip |
| spellingShingle | Pierre Caron Jonathan Choudjaye Thomas Clouaire Béatrix Bugler Virginie Daburon Marion Aguirrebengoa Thomas Mangeat Jason S. Iacovoni Alejandro Álvarez-Quilón Felipe Cortés-Ledesma Gaëlle Legube Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks Cell Reports DSB repair chromatin PI 3-kinases γH2AX ChIP-chip |
| title | Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks |
| title_full | Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks |
| title_fullStr | Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks |
| title_full_unstemmed | Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks |
| title_short | Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks |
| title_sort | non redundant functions of atm and dna pkcs in response to dna double strand breaks |
| topic | DSB repair chromatin PI 3-kinases γH2AX ChIP-chip |
| url | http://www.sciencedirect.com/science/article/pii/S221112471501178X |
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