CHROMOSOMAL INSTABILITY AND DNA REPAIR MECHANISMS IN GENOME INTEGRITY MAINTENANCE

Abstract

The cellular functioning and the accurate transmission of genetic information require genome integrity. Nonetheless, chronic exposures to endogenous and exogenous stimuli cause DNA damage and chromosomal instability (CIN), which is one of the signs of most human diseases. CIN involves numerical and structural changes in the chromosomes and is intimately linked with cancer, genetic and aging. This review provides a summary of the molecular pathways involved in chromosomal instability and the molecular pathways of DNA damage response (DDR) homeostatic mechanisms. The major DNA repair processes, such as base excision repair, nucleotide excision repair, mismatch repair, homologous recombination, and non-homologous end joining are mentioned in the context of their interactions. Its role in the progression of a disease is mentioned, and the interaction between the defective DNA repair and CIN propagation is brought to light. Recent discoveries in the field of genomic technologies and experimental techniques have enhanced our cognitions of genome maintenance processes. Also, DNA repair pathways treatment, including synthetic lethality and activity of PARP, are considered. With all this, the issue with understanding the complexity of the genome stability networks still exists. On the whole, this review synthesizes existing knowledge, reveals the gaps in the research, and provides future directions related to enhancing the integrity of genomes and managing diseases.