Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation.

Human glioblastomas are characterized by frequent DNA amplifications most often at chromosome regions 7p11.2 and 12q13-15. Although amplification is a well-known hallmark of glioblastoma genetics the function of most amplified genes in glioblastoma biology is not understood.

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

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.

ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2.

Homologous recombination (HR) and non-homologous end joining (NHEJ) represent distinct pathways for repairing DNA double-strand breaks (DSBs). Previous work implicated Artemis and ATM in an NHEJ-dependent process, which repairs a defined subset of radiation-induced DSBs in G1-phase. Here, we show that in G2, as in G1, NHEJ represents the major DSB-repair pathway whereas HR is only essential for repair of approximately 15% of X- or gamma-ray-induced DSBs.

Radiation-induced HPRT mutations resulting from misrejoined DNA double-strand breaks.

DNA double-strand breaks (DSBs) are the most severe lesions induced by ionizing radiation, and unrejoined or misrejoined DSBs can lead to cell lethality, mutations and the initiation of tumorigenesis. We have investigated X-ray- and alpha-particle-induced mutations that inactivate the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene in human bladder carcinoma cells and in hTERT-immortalized human fibroblasts. Fifty to 80% of the mutants analyzed exhibited partial or total deletions of the 9 exons of the HPRT locus.