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    DNA replication, recombination, and repair are highly interconnected processes the disruption of which must be coordinated in cancer. HERC2, a large HECT protein required for homologous recombination repair, is an E3 ubiquitin ligase that targets breast cancer suppressor BRCA1 for degradation. Here, we show that HERC2 is a component of the DNA replication fork complex that plays a critical role in DNA elongation and origin firing. In the presence of BRCA1, endogenous HERC2 interacts with Claspin, a protein essential for G2–M checkpoint activation and replication fork stability. Claspin depletion slowed S-phase progression and additional HERC2 depletion reduced the effect of Claspin depletion. In addition, HERC2 interacts with replication fork complex proteins. Depletion of HERC2 alleviated the slow replication fork progression in Claspin-deficient cells, suppressed enhanced origin firing, and led to a decrease in MCM2 phosphorylation. In a HERC2-dependent manner, treatment of cells with replication inhibitor aphidicolin enhanced MCM2 phosphorylation. Taken together, our results suggest that HERC2 regulates DNA replication progression and origin firing by facilitating MCM2 phosphorylation. These findings establish HERC2 as a critical function in DNA repair, checkpoint activation, and DNA replication. Cancer Res; 71(17); 5621–5. ©2011 AACR.
    cancerres.aacrjournals.org   ...Read On

    (Washington University School of Medicine) A new study shows that donations collected by check boxes on state income tax forms, fees from license plates and revenue from state lottery tickets have raised millions for breast cancer research and prevention programs across the country, according to researchers at Washington University in St. Louis.
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    Screening for mutations in a gene known as CHEK2 may help determine a woman's odds of breast cancer if the disease runs in her family
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    Screening for mutations in a gene known as CHEK2 may help determine a woman's odds of breast cancer if the disease runs in her family
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    photo(AP) - FILE - In this June 8, 2011 file photo, Martina McBride arrives at the 2011 CMT Music Awards in Nashville, Tenn. 'Good Morning America' anchor Robin Roberts, singer Sheryl Crow, ABC's Katie Couric and 'Today' anchor Hoda Kotb all appear in the video for McBride's song about cancer, ''I'm Gonna Love You Through It' which debuts on CMT.com on Wednesday, Aug. 17. Roberts, Crow and Kotb are all survivors of breast cancer, while Couric's husband died of colon cancer.(AP Photo/Charles Sykes, file)


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