Role of specialized DNA polymerases in the limitation of replicative stress and DNA damage transmission

Genomic instability in fragile sites—still adding the pieces

“…This region contains four long AT-rich flexibility sequences (>400 bp). 71 The analysis revealed a slower replication rate and a shorter origin distance at the FS region Specialized DNA polymerases have a role in the rescue of stalled replication forks, primarily by contributing to S-phase checkpoint activation (reviewed in the study by Bournique et al 69 ). Initially, when replication forks encounter barriers, the replicative DNA polymerase progression is blocked, whereas helicases continue to advance along the DNA, generating long stretches of ssDNA which recruit the binding protein replication protein A (RPA).…”

Transcriptional Changes of DNA Replication and Repair Factors Over Uveal Melanoma Subtypes

“…The expression levels of POLD1 and POLE support a recently proposed model [44] in which a switch to POL  and away from POL occurs upon DNA damage. We have not yet addressed the behavior of POL , or of the specialized polymerases that recently have been hypothesized to assist the replication machinery in the prevention of replication stress [4].…”

“…In the "R" environment (https://cran.cnr.berkeley.edu/) Z scores were calculated for each exon of each gene by mean-centering, using the tumor cohort as average, the log2 transformed RPKM values and dividing by the standard deviation, visualizing high (red), no change/no expression (white), and low (blue) and arranging data by UVM cluster assignments (1)(2)(3)(4) in heat maps.…”

“…UVM cases were sorted into two groups, those with average Z scores "Above" and those "Below" zero. After group designation, the cluster (1)(2)(3)(4) each case belonged to was identified and the numbers of cases "High" and "Low" for each cluster counted and displayed graphically using GraphPad Prism 6. Significant differences between "1 and 2" versus "3 and 4" were determined by Fisher's exact (two tailed), using GraphPad Quick Calcs.…”

“…Replication stress is thought to be an early and strong driving force in tumorigenesis. It is defined as impediment to the replication fork that causes slowing or stalling of the replication machinery and is brought on by a variety of factors broadly classified as "exogenous" and "endogenous" [4]. Examples of exogenous causes are radiation, therapeutic treatment, and diet, where endogenous causes are DNA structures, protein-DNA complexes, nucleotide pool availability, reactive oxidation species, transcription and replication complex collision, and mutation and expression alteration in tumor suppressor and oncogenes.…”