γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity

Many toxic agents can cause DNA double strand breaks (DSBs), which are in most cases quickly repaired by the cellular machinery. Using ionising radiation, we explored the kinetics of DNA lesion signaling and structural chromosome aberration formation at the intra- and inter-chromosomal level. Using...

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Main Authors: Michelle Ricoul, Tamizh Selvan Gnana Sekaran, Patricia Brochard, Cecile Herate, Laure Sabatier
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/11/9/1397
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author Michelle Ricoul
Tamizh Selvan Gnana Sekaran
Patricia Brochard
Cecile Herate
Laure Sabatier
author_facet Michelle Ricoul
Tamizh Selvan Gnana Sekaran
Patricia Brochard
Cecile Herate
Laure Sabatier
author_sort Michelle Ricoul
collection DOAJ
description Many toxic agents can cause DNA double strand breaks (DSBs), which are in most cases quickly repaired by the cellular machinery. Using ionising radiation, we explored the kinetics of DNA lesion signaling and structural chromosome aberration formation at the intra- and inter-chromosomal level. Using a novel approach, the classic Premature Chromosome Condensation (PCC) was combined with γ-H2AX immunofluorescence staining in order to unravel the kinetics of DNA damage signalisation and chromosome repair. We identified an early mechanism of DNA DSB joining that occurs within the first three hours post-irradiation, when dicentric chromosomes and chromosome exchanges are formed. The slower and significant decrease of ”deleted chromosomes” and 1 acentric telomere fragments observed until 24 h post-irradiation, leads to the conclusion that a second and error-free repair mechanism occurs. In parallel, we revealed remaining signalling of γ-H2AX foci at the site of chromosome fusion long after the chromosome rearrangement formation. Moreover there is important signalling of foci on the site of telomere and sub-telomere sequences suggesting either a different function of γ-H2AX signalling in these regions or an extreme sensibility of the telomere sequences to DNA damage that remains unrepaired 24 h post-irradiation. In conclusion, chromosome repair happens in two steps, including a last and hardly detectable one because of restoration of the chromosome integrity.
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spelling doaj.art-59b97aacc97f4aed86a888264d3b82d02023-09-02T12:57:32ZengMDPI AGCancers2072-66942019-09-01119139710.3390/cancers11091397cancers11091397γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome IntegrityMichelle Ricoul0Tamizh Selvan Gnana Sekaran1Patricia Brochard2Cecile Herate3Laure Sabatier4PROCyTox, French Alternative Energies and Atomic Energy Commission (CEA), Paris-Saclay University, 92260 Fontenay-aux-Roses, FrancePROCyTox, French Alternative Energies and Atomic Energy Commission (CEA), Paris-Saclay University, 92260 Fontenay-aux-Roses, FrancePROCyTox, French Alternative Energies and Atomic Energy Commission (CEA), Paris-Saclay University, 92260 Fontenay-aux-Roses, FrancePROCyTox, French Alternative Energies and Atomic Energy Commission (CEA), Paris-Saclay University, 92260 Fontenay-aux-Roses, FrancePROCyTox, French Alternative Energies and Atomic Energy Commission (CEA), Paris-Saclay University, 92260 Fontenay-aux-Roses, FranceMany toxic agents can cause DNA double strand breaks (DSBs), which are in most cases quickly repaired by the cellular machinery. Using ionising radiation, we explored the kinetics of DNA lesion signaling and structural chromosome aberration formation at the intra- and inter-chromosomal level. Using a novel approach, the classic Premature Chromosome Condensation (PCC) was combined with γ-H2AX immunofluorescence staining in order to unravel the kinetics of DNA damage signalisation and chromosome repair. We identified an early mechanism of DNA DSB joining that occurs within the first three hours post-irradiation, when dicentric chromosomes and chromosome exchanges are formed. The slower and significant decrease of ”deleted chromosomes” and 1 acentric telomere fragments observed until 24 h post-irradiation, leads to the conclusion that a second and error-free repair mechanism occurs. In parallel, we revealed remaining signalling of γ-H2AX foci at the site of chromosome fusion long after the chromosome rearrangement formation. Moreover there is important signalling of foci on the site of telomere and sub-telomere sequences suggesting either a different function of γ-H2AX signalling in these regions or an extreme sensibility of the telomere sequences to DNA damage that remains unrepaired 24 h post-irradiation. In conclusion, chromosome repair happens in two steps, including a last and hardly detectable one because of restoration of the chromosome integrity.https://www.mdpi.com/2072-6694/11/9/1397chromosomepremature chromosome condensationγ-H2AXdicentric chromosomeDNA repairtelomereirradiation
spellingShingle Michelle Ricoul
Tamizh Selvan Gnana Sekaran
Patricia Brochard
Cecile Herate
Laure Sabatier
γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity
Cancers
chromosome
premature chromosome condensation
γ-H2AX
dicentric chromosome
DNA repair
telomere
irradiation
title γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity
title_full γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity
title_fullStr γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity
title_full_unstemmed γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity
title_short γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity
title_sort γ h2ax foci persistence at chromosome break suggests slow and faithful repair phases restoring chromosome integrity
topic chromosome
premature chromosome condensation
γ-H2AX
dicentric chromosome
DNA repair
telomere
irradiation
url https://www.mdpi.com/2072-6694/11/9/1397
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