The establishment of connections between biochemical defects and clinical disease is a major goal of modern molecular genetics. In this review, we examine the current literature that relates defects in the two major DNA double-strand-break repair pathways--homologous recombination and nonhomologous end-joining--with the development of human tumors. Although definitive proof has yet to be obtain...

The integrity of genomic DNA is crucial for its function. And yet, DNA in living cells is inherently unstable. It is subject to mechanical stress and to many types of chemical modification that may lead to breaks in one or both strands of the double helix. Within the cell, reactive oxygen species generated by normal respiratory metabolism can cause double-strand breaks, as can stalled DNA repli...

Clinically used bleomycin A5 has been employed in a study of double-strand cleavage of a library of 10 hairpin DNAs originally selected on the basis of their strong binding to bleomycin. Each of the DNAs underwent double-strand cleavage at more than one site, and all of the cleavage sites were within, or in close proximity to, an eight-base-pair region of the duplex that had been randomized to ...

Oligomeric porphyrin arrays with an alternating pyridyl–porphyrin sequence were synthesized to explore double-strand formation through self-complementary pyridyl-to-zinc axial coordination bonds. Competitive titration experiments revealed the thermodynamic aspects involved in the zipper effect within double-strand formation. Multiple axial coordination bonds defined the stacked conformation, de...

The conversion of a nucleic acid from single strands to double strands is thought to involve slow nucleation followed by fast double-strand propagation. Here, for RNA double-strand propagation, we propose an atomic resolution reaction mechanism. This mechanism, called the stack-ratchet, is based on data-mining of three-dimensional structures and on available thermodynamic information. The stack...

An alkaline elution procedure was used to study the nature of DNA damage induced by auromomycin, an antitumor protein, in human leukemic lymphoblasts (CCRF-CEM cells). The filter elu tion of drug-treated cells at pH 12.2 and 9.6 showed induction of both single and double strand DNA breaks. The DNA strand scission activities were linear in relation to drug concentration. The frequency of single ...

Topoisomerase I cleavage complexes can be induced by a variety of DNA damages and by the anticancer drug camptothecin. We have developed a ligation-mediated PCR (LM-PCR) assay to analyze replication-mediated DNA double-strand breaks induced by topoisomerase I cleavage complexes in human colon carcinoma HT29 cells at the nucleotide level. We found that conversion of topoisomerase I cleavage comp...

Combining green fluorescent protein with a protein that only binds to double strand breaks in DNA allows these breaks-which are an important form of DNA damage-to be detected with high efficiency in living bacteria.

ownloade C regulates a myriad of genes controlling cell proliferation, metabolism, differentiation, and apoptosis. lso controls the expression of DNA double-strand break (DSB) repair genes and therefore may be a ial target for anticancer therapy to sensitize cancer cells to DNA damage or prevent genetic instability. report, we studied whether MYC binds to DSB repair gene promoters and modulates...