Recognition of Damaged DNA: Structure and Dynamic Markers

Abstract

DNA damage, a consequence of external factors and inherent metabolic processes, is omnipresent. Nature has devised multiple strategies to safeguard the genetic information and developed intricate repair mechanisms and pathways to reverse an array of different DNA lesions, including mismatches. Failure of the DNA repair systems may result in mutation, premature ageing, and cancer. In this review, we focus on structural and dynamic aspects of detection of lesions in base excision and mismatch repair. A thorough understanding of repair, pathways, and regulation is necessary to develop strategies for targeting DNA-related pathologies.

E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

“…One single-stranded DNA genome is generated each time a double-stranded DNA genome is used as a template (Knipe, 2006). These DNA structures can stimulate a robust DNA-damage response (Germann et al, 2010; Peterson and Cote, 2004). We previously reported that viral genome replication leads to widespread phosphorylation of H2AX, suggesting that the infected cell experiences a diffusely distributed genotoxic signal (Nichols et al, 2009).…”

Orientation-dependent FRET system reveals differences in structures and flexibilities of nicked and gapped DNA duplexes

“…Recent studies have indicated that DNA-binding proteins can recognize differences in structures and flexibilities of DNA duplexes (1,2). X-ray crystallography and nuclear magnetic resonance (NMR) are powerful tools for analysis of DNA structures, but these techniques require a large amount of sample and are time consuming.…”

Spectral Self-Interference Fluorescence Microscopy to Study Conformation of Biomolecules with Nanometer Accuracy

“…For the short patch repair, the phosphodiester bond at 3′ of the abasic site is cleaved by glycosylate, and the 5′ bond is incised by APE1 endonuclease, which then recruits DNA polymerase to fill the gap that is ligated by a DNA-ligase complex. During the process of BER, the conformation and flexibility of DNA changes with the binding of different enzymes, which kinks the DNA to different angles [168][169][170][171][172][173][174][175]. Through careful design of experiments, the SSFM platform can potentially detect DNA BER through direct detection of DNA conformational changes and protein-binding events.…”