Women having BRCA1 germ-line mutations develop cancer in breast and ovary, estrogen-regulated tissues, with high penetrance. Binding of estrogens to the estrogen receptor (ER) transiently induces DNA double-strand breaks (DSBs) by topoisomerase II (TOP2) and controls gene transcription. TOP2 resolves catenated DNA by transiently generating DSBs, TOP2-cleavage complexes (TOP2ccs), where TOP2 covalently binds to 5′ ends of DSBs. TOP2 frequently fails to complete its catalysis, leading to formation of pathological TOP2ccs. We have previously shown that the endonucleolytic activity of MRE11 plays a key role in removing 5′ TOP2 adducts in G1phase. We show here that BRCA1 promotes MRE11-mediated removal of TOP2 adducts in G1phase. We disrupted theBRCA1gene in53BP1-deficient ER-positive breast cancer and B cells. The loss of BRCA1 caused marked increases of pathological TOP2ccs in G1phase following exposure to etoposide, which generates pathological TOP2ccs. We conclude that BRCA1 promotes the removal of TOP2 adducts from DSB ends for subsequent nonhomologous end joining.BRCA1-deficient cells showed a decrease in etoposide-induced MRE11 foci in G1phase, suggesting that BRCA1 repairs pathological TOP2ccs by promoting the recruitment of MRE11 to TOP2cc sites. BRCA1 depletion also leads to the increase of unrepaired DSBs upon estrogen treatment both in vitro in G1-arrested breast cancer cells and in vivo in epithelial cells of mouse mammary glands. BRCA1 thus plays a critical role in removing pathological TOP2ccs induced by estrogens as well as etoposide. We propose that BRCA1 suppresses tumorigenesis by removing estrogen-induced pathological TOP2ccs throughout the cell cycle.

The characteristics of bismuth-doped glasses were investigated as colorless ultrabroadband near-infrared gain media. The colorless Bi-doped soda-lime-silicate glass was prepared under controlled redox conditions, and it realized the broadest near-infrared emission of about 600nm in full width at half maximum, centered at 1000nm, under 720nm excitation. The emission band extended toward shorter wavelengths compared with the shortest wavelength for the Bi-doped glass ever reported. The colorless Bi-doped glass developed in this work has a good potential for the broadband gain media for amplifiers and tunable lasers.

The luminescence characteristics of Te-and Bi-doped glasses and glass-ceramics were investigated and the origin of coloration and near infrared luminescence was discussed. The colorations of these glasses and glass-ceramics might be due to the elemental clustering, such as Te 2 Te 2 and Bi 2 Bi 2 . The broad near infrared NIR luminescence can be detected in Te-and Bi-doped glasses and glass-ceramics. The electron spin resonance ESR signal at Ŏ ŋ2.0 was observed in Te-and Bi-doped glasses and glass-ceramics, which exhibit NIR luminescence, and therefore this ESR signal is strongly related to the NIR luminescence. The ESR signal at Ŏ ŋ2.0 might be derived from molecular ions of Te and Bi, Te 2 and Bi 2 . Consequently, it is suggested that the broad NIR luminescence of Te-and Bi-doped glass and glass-ceramics are most likely to be caused by elemental clustering, such as Te 2 Te 2 and Bi 2 Bi 2 .

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