Summary DNA interstrand cross-links (ICLs) are toxic DNA lesions whose repair occurs in the S phase of metazoans via an unknown mechanism. Here, we describe a novel cell-free system based on Xenopus egg extracts that supports ICL repair. During DNA replication of a plasmid containing a site-specific ICL, two replication forks converge on the cross-link. Subsequent lesion bypass involves advance of a nascent leading strand to within one nucleotide of the ICL, followed by incisions, translesion DNA synthesis, and extension of the nascent strand beyond the lesion. Immunodepletion experiments suggest that extension requires DNA polymeras ζ Ultimately, a significant portion of the input DNA is fully repaired, but not if DNA replication is blocked. Repair in this system is accompanied by activation of the Fanconi anemia and ATR checkpoint pathways. Our experiments establish a mechanism for ICL repair that reveals how this process is coupled to DNA replication.

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DNA interstrand cross-links (ICLs) are the clinically most relevant adducts formed by many antitumor agents. To facilitate the study of biological responses triggered by ICLs, we developed a new approach toward the synthesis of mimics of nitrogen mustard ICLs. 7-Deazaguanine residues bearing acetaldehyde groups were incorporated into complementary strands of DNA and cross-link formation induced by double reductive amination. Our strategy enables the synthesis of major groove cross-links in high yields and purity.

We search for neutral heavy leptons that are isosinglets under the standard SU (2)l gauge group. Such neutral heavy leptons are expected in many extensions of the standard model. Three types of heavy leptons Ne, N^, NT associated with the three neutrino types v* have been directly searched for and no evidence for a signal has been found. We set the limit Br(Z° -► z//N*) < 3 x 10" 5 at the 95% CL for the mass range from 3 GeV up to m%.

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