Bloom Syndrome

Scientists at National Cancer Institute detail research in cancer

Bloom Syndrome Library Library Home This article was published in Clinical Oncology Week, which you can subscribe to online.

"Here, we report that BLM-deficient cell lines and primary fibroblasts display an endogenously activated DNA double-strand break checkpoint response with prominent levels of phosphorylated histone H2AX (gamma-H2AX), Chk2 (p(T68)Chk2), and ATM (p(S1981)ATM) colocalizing in nuclear foci. Interestingly, the mitotic fraction of gamma-H2AX foci did not seem to be higher in BLM-deficient cells, indicating that these lesions form transiently during interphase. Pulse labeling with iododeoxyuridine and immunofluorescence microscopy showed the colocalization of gamma-H2AX, ATM, and Chk2 together with replication foci. Those foci costained for Rad51, indicating homologous recombination at these replication sites. We therefore analyzed replication in BS cells using a single molecule approach on combed DNA fibers. In addition to a higher frequency of replication fork barriers, BS cells displayed a reduced average fork velocity and global reduction of interorigin distances indicative of an elevated frequency of origin firing. Because BS is one of the most penetrant cancer-predisposing hereditary diseases, it is likely that the lack of BLM engages the cells in a situation similar to precancerous tissues with replication stress," wrote V.A. Rao and colleagues, National Cancer Institute.

The researchers concluded: "To our knowledge, this is the first report of high ATM-Chk2 kinase activation and its linkage to replication defects in a BS model."

Rao and colleagues published their study in Molecular Cancer Research (Endogenous {gamma}-H2AX-ATM-Chk2 checkpoint activation in Bloom's syndrome helicase deficient cells is related to DNA replication arrested forks. Molecular Cancer Research, 2007;5(7):713-24).

For additional information, contact V.A. Rao, Laboratory of Molecular Pharmacology, US Dept. of Health and Human Services, National Cancer Institute, Bethesda, Bethesda, Maryland USA..

The publisher's contact information for the journal Molecular Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

Keywords: United States, Bethesda, Bloom Syndrome, Cancer, Cancer Research, DNA, DNA Replication, DNA Research, Enzyme Research, Helicase, Medical Device, Oncology.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.