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Open AccessArticle

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

PROCyTox, French Alternative Energies and Atomic Energy Commission (CEA), Paris-Saclay University, 92260 Fontenay-aux-Roses, France
*
Author to whom correspondence should be addressed.
Current Address: Central Research Lab, K S Hegde Medical Academy, NITTE (Deemed to be University), 575018 Mangalore, India.
Cancers 2019, 11(9), 1397; https://doi.org/10.3390/cancers11091397
Received: 9 August 2019 / Revised: 13 September 2019 / Accepted: 17 September 2019 / Published: 19 September 2019
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. View Full-Text
Keywords: chromosome; premature chromosome condensation; γ-H2AX; dicentric chromosome; DNA repair; telomere; irradiation chromosome; premature chromosome condensation; γ-H2AX; dicentric chromosome; DNA repair; telomere; irradiation
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MDPI and ACS Style

Ricoul, M.; Gnana Sekaran, T.S.; Brochard, P.; Herate, C.; Sabatier, L. γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity. Cancers 2019, 11, 1397.

AMA Style

Ricoul M, Gnana Sekaran TS, Brochard P, Herate C, Sabatier L. γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity. Cancers. 2019; 11(9):1397.

Chicago/Turabian Style

Ricoul, Michelle; Gnana Sekaran, Tamizh S.; Brochard, Patricia; Herate, Cecile; Sabatier, Laure. 2019. "γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity" Cancers 11, no. 9: 1397.

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