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Elevated radiation-induced γH2AX foci in G2 phase heterozygous BRCA2 fibroblasts.

Beucher, Andrea and Deckbar, Dorothee and Schumann, Eik and Krempler, Andrea and Frankenberg-Schwager, Marlis and Löbrich, Markus :
Elevated radiation-induced γH2AX foci in G2 phase heterozygous BRCA2 fibroblasts.
In: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 101 (1) pp. 46-50. ISSN 1879-0887
[Article] , (2011)

Abstract

BACKGROUND AND PURPOSE: About 5-10% of all breast cancer cases are associated with heterozygous germ-line mutations in the genes encoding BRCA1 and BRCA2. Carriers of such mutations are highly predisposed for developing breast or ovarian cancer and, thus, are advised to undergo regular radio-diagnostic examinations. BRCA1 and BRCA2 are involved in multiple cellular processes including the repair of ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) and different studies addressing the DSB repair capacity of BRCA1+/- or BRCA2+/- cells led to contradictory results. MATERIALS AND METHODS: Using the sensitive method of γH2AX foci analysis in combination with cell cycle markers, we specifically measured DSB repair in confluent G0 as well as in exponentially growing G1 and G2 phase primary WT, BRCA1+/- and BRCA2+/- fibroblasts. RESULTS: Both BRCA1+/- and BRCA2+/- cells displayed normal DSB repair in G0 and in G1. In contrast, in G2, BRCA2+/- but not BRCA1+/- cells exhibited a decreased DSB repair capacity which was in between that of WT and that of a hypomorphic BRCA2-/- cell line. CONCLUSIONS: The residual amount of normal BRCA1 seems to be sufficient for efficient DSB repair in all cell cycle phases, while the decreased DSB repair capacity of heterozygous BRCA2 mutations suggests gene dosage effects in G2.

Item Type: Article
Erschienen: 2011
Creators: Beucher, Andrea and Deckbar, Dorothee and Schumann, Eik and Krempler, Andrea and Frankenberg-Schwager, Marlis and Löbrich, Markus
Title: Elevated radiation-induced γH2AX foci in G2 phase heterozygous BRCA2 fibroblasts.
Language: English
Abstract:

BACKGROUND AND PURPOSE: About 5-10% of all breast cancer cases are associated with heterozygous germ-line mutations in the genes encoding BRCA1 and BRCA2. Carriers of such mutations are highly predisposed for developing breast or ovarian cancer and, thus, are advised to undergo regular radio-diagnostic examinations. BRCA1 and BRCA2 are involved in multiple cellular processes including the repair of ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) and different studies addressing the DSB repair capacity of BRCA1+/- or BRCA2+/- cells led to contradictory results. MATERIALS AND METHODS: Using the sensitive method of γH2AX foci analysis in combination with cell cycle markers, we specifically measured DSB repair in confluent G0 as well as in exponentially growing G1 and G2 phase primary WT, BRCA1+/- and BRCA2+/- fibroblasts. RESULTS: Both BRCA1+/- and BRCA2+/- cells displayed normal DSB repair in G0 and in G1. In contrast, in G2, BRCA2+/- but not BRCA1+/- cells exhibited a decreased DSB repair capacity which was in between that of WT and that of a hypomorphic BRCA2-/- cell line. CONCLUSIONS: The residual amount of normal BRCA1 seems to be sufficient for efficient DSB repair in all cell cycle phases, while the decreased DSB repair capacity of heterozygous BRCA2 mutations suggests gene dosage effects in G2.

Journal or Publication Title: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Volume: 101
Number: 1
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
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10 Department of Biology
Date Deposited: 27 Jun 2011 06:47
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