Brosh R.M.Jr. (ed.) DNA Replication Stress

MDPI, 2019. — 370 p.During DNA synthesis in vivo, the replication fork encounters a variety of forms of stress imposed by DNA damage, alternate DNA structures, genetic deficiency, and pharmacologically-induced conditions that ultimately impede fork progression and may lead to the elicitation of signaling cascades. Covalent lesions induced by environmental exposure or from endogenous biochemical processes as well as noncovalent modifications introduced by DNA binding compounds perturb fork advancement and stability. Similarly, DNA structures, such as hairpins or G-quadruplexes, which deviate from the noncanonical B-form duplex DNA, can be problematic for the replisome machinery. Collisions of the replisome with transcription complexes or other protein-DNA complexes may lead to replication stress. Inhibition of DNA polymerase-catalyzed DNA synthesis or depletion of the nucleotide pool by certain chemical agents stalls the replication fork as well. Genetic deficiency or depletion of key DNA metabolic proteins, or inhibition of molecular functions of key proteins associated with the replisome can also be a source of DNA replication stress. To contend with these and other forms of replication stress, eukaryotic cells possess a number of mechanisms involving DNA damage response or DNA repair proteins as well as cell cycle checkpoints to help mediate the appropriate response. This IJMS Special Issue on “DNA Replication Stress” will address these mechanisms, mediated at the molecular and cellular levels, to respond to adverse genomic perturbations and cellular conditions so that chromosomal stability and cellular homeostasis is maintained.