Lack of spontaneous and radiation-induced chromosome breakage at interstitial telomeric sites in murine scid cells

2004 ◽  
Vol 104 (1-4) ◽  
pp. 131-136 ◽  
Author(s):  
H.-P. Wong ◽  
H. Mozdarani ◽  
C. Finnegan ◽  
J. McIlrath ◽  
P.E. Bryant ◽  
...  
Keyword(s):  
Chromosome Breakage ◽  
Radiation Induced ◽  
Interstitial Telomeric Sites ◽  
I Cells

scholarly journals Homozygous hypomorphic BRCA2 variant in primary ovarian insufficiency without cancer or Fanconi anaemia trait

2020 ◽  
pp. jmedgenet-2019-106672 ◽  
Author(s):  
Sandrine Caburet ◽  
Abdelkader Heddar ◽  
Elodie Dardillac ◽  
Héléne Creux ◽  
Marie Lambert ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Public Health Problem ◽  
Chromosome Breakage ◽  
Primary Ovarian Insufficiency ◽  
Fanconi Anaemia ◽  
Ovarian Insufficiency ◽  
Her Family ◽  
Functional Studies ◽  
Chromosomal Breaks ◽  
Radiation Induced

BackgroundPrimary ovarian insufficiency (POI) affects 1% of women under 40 years and is a public health problem. The genetic causes of POI are highly heterogeneous with isolated or syndromic forms. Recently, variants in genes involved in DNA repair have been shown to cause POI. Notably, syndromic POI with Fanconi anaemia (FA) traits related to biallelic BRCA2 truncated variants has been reported. Here, we report a novel phenotype of isolated POI with a BRCA2 variant in a consanguineous Turkish family.MethodsExome sequencing (ES) was performed in the patient. We also performed functional studies, including a homologous recombination (HR) test, cell proliferation, radiation-induced RAD51 foci formation assays and chromosome breakage studies in primary and lymphoblastoid immortalised cells. The expression of BRCA2 in human foetal ovaries was studied.ResultsES identified a homozygous missense c.8524C>T/p.R2842C-BRCA2 variant. BRCA2 defects induce cancer predisposition and FA. Remarkably, neither the patient nor her family exhibited somatic pathologies. The patient’s cells showed intermediate levels of chromosomal breaks, cell proliferation and radiation-induced RAD51 foci formation compared with controls and FA cells. R2842C-BRCA2 only partially complemented HR efficiency compared with wild type-BRCA2. BRCA2 is expressed in human foetal ovaries in pachytene stage oocytes, when meiotic HR occurs.ConclusionWe describe the functional assessment of a homozygous hypomorphic BRCA2 variant in a patient with POI without cancer or FA trait. Our findings extend the phenotype of BRCA2 biallelic alterations to fully isolated POI. This study has a major impact on the management and genetic counselling of patients with POI.

scholarly journals Role of ATM and the Damage Response Mediator Proteins 53BP1 and MDC1 in the Maintenance of G2/M Checkpoint Arrest

2010 ◽  
Vol 30 (13) ◽  
pp. 3371-3383 ◽  
Author(s):  
Atsushi Shibata ◽  
Olivia Barton ◽  
Angela T. Noon ◽  
Kirsten Dahm ◽  
Dorothee Deckbar ◽  
...  
Keyword(s):  
Chromosome Breakage ◽  
Nonhomologous End Joining ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Radiation Induced ◽  
High Doses ◽  
Interfering Rna ◽  
Atm Signaling

ABSTRACT ATM-dependent initiation of the radiation-induced G2/M checkpoint arrest is well established. Recent results have shown that the majority of DNA double-strand breaks (DSBs) in G2 phase are repaired by DNA nonhomologous end joining (NHEJ), while ∼15% of DSBs are slowly repaired by homologous recombination. Here, we evaluate how the G2/M checkpoint is maintained in irradiated G2 cells, in light of our current understanding of G2 phase DSB repair. We show that ATM-dependent resection at a subset of DSBs leads to ATR-dependent Chk1 activation. ATR-Seckel syndrome cells, which fail to efficiently activate Chk1, and small interfering RNA (siRNA) Chk1-treated cells show premature mitotic entry. Thus, Chk1 significantly contributes to maintaining checkpoint arrest. Second, sustained ATM signaling to Chk2 contributes, particularly when NHEJ is impaired by XLF deficiency. We also show that cells lacking the mediator proteins 53BP1 and MDC1 initially arrest following radiation doses greater than 3 Gy but are subsequently released prematurely. Thus, 53BP1 −/− and MDC1 −/− cells manifest a checkpoint defect at high doses. This failure to maintain arrest is due to diminished Chk1 activation and a decreased ability to sustain ATM-Chk2 signaling. The combined repair and checkpoint defects conferred by 53BP1 and MDC1 deficiency act synergistically to enhance chromosome breakage.

Spontaneous and radiation-induced chromosomal breakage at interstitial telomeric sites

Chromosoma ◽  
1996 ◽  
Vol 104 (8) ◽  
pp. 596-604 ◽  
Author(s):  
P. Slijepcevic ◽  
Y. Xiao ◽  
I. Dominguez ◽  
A. T. Natarajan
Keyword(s):  
Chromosomal Breakage ◽  
Radiation Induced ◽  
Interstitial Telomeric Sites

Radiation-induced non-random chromosome breakage

1972 ◽  
Vol 75 (2) ◽  
pp. 541-543 ◽  
Author(s):  
T. Caspersson ◽  
Ulla Haglund ◽  
B. Lindell ◽  
Lore Zech
Keyword(s):  
Chromosome Breakage ◽  
Radiation Induced

Flagyl and radiation-induced chromosome breakage

1978 ◽  
Vol 51 (608) ◽  
pp. 654-655 ◽  
Author(s):  
J. S. Prosser ◽  
C. M. White
Keyword(s):  
Chromosome Breakage ◽  
Radiation Induced
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