Formation and Repair of an Interstrand DNA Cross-Link Arising from a Common Endogenous Lesion

• DOI: 10.1021/jacs.1c06926
• Publication Date: 2021-09-13T21:34:15Z
• Authors: Kurt Housh; Jay S. Jha; Zhiyu Yang; Tuhin Haldar; Kevin M. Johnson; Jiekai Yin; Yinsheng Wang; Kent S. Gates
• Keywords: Cross-link; Link (geometry)

Interstrand DNA cross-links (ICLs) are cytotoxic because they block the strand separation required for read-out and replication of genetic information in duplex DNA. The unavoidable formation ICLs cellular may contribute to aging, neurodegeneration, cancer. Here, we describe properties a structurally complex ICL derived from an apurinic/apyrimidinic (AP) site, which is one most common endogenous lesions results characterize cross-link arising aza-Michael addition N2-amino group guanine residue electrophilic sugar remnant generated by spermine-mediated cleavage at AP site An α,β-unsaturated iminium ion critical intermediate involved formation. Studies employing bacteriophage φ29 polymerase provided evidence that this can transactions require separation. biochemical studies suggest break/ICL might be repaired simple mechanism 3′-exonuclease action enzyme endonuclease (APE1) unhooks initiate repair via single-strand break pathway.