DNADamage: Sensing

Abstract

Maintenance of genomic stability is essential for the survival of cells, organisms, and species. Genomic stability relies on the complete and accurate transmission of genetic materials from mother cells to daughter cells and from one generation to the next. This task is daunting, however, because the genome is constantly challenged by numerous intrinsic and extrinsic stresses that damage deoxyribonucleic acid (DNA). If left untreated, such damage can destabilize the genome by introducing gene mutations, duplications, and chromosomal rearrangements such as deletions and inversions, which fortunately does not normally happen as cells evolve a complex damage sensing and signaling mechanism named the DNA damage and replication checkpoint. Checkpoint activation effectively pauses the progression of the cell cycle, allowing more time for the removal of DNA lesion. Moreover, activated checkpoint also regulates and coordinates a number of cellular processes including DNA repair, DNA replication, and chromatin remodeling to alleviate the stress on the genome. At the core of the checkpoint‐signaling network, a family of phosphoinositide‐3‐kinase (PI‐3K)‐like kinases and their regulatory partners serve as both DNA damage sensors and initiators of checkpoint signaling. In this article, we will discuss in detail how DNA damage is sensed and processed by the DNA damage and replication checkpoint. We will also discuss how signals generated at sites of DNA damage are propagated and relayed through the checkpoint pathways to influence other cellular events.

Novel, Broad Spectrum Anticancer Agents Containing the Tricyclic 5:7:5-Fused Diimidazodiazepine Ring System

“…Damaged genes are ultimately responsible for the loss of growth control mechanisms leading to out of control cell proliferation 2. When cells are damaged beyond repair, they are normally eliminated by apoptosis, but cancer cells avoid apoptosis and continue to undergo unregulated cell division 3.…”

“…1 Damaged genes are ultimately responsible for the loss of growth control mechanisms leading to out of control cell proliferation. 2 When cells are damaged beyond repair, they are normally eliminated by apoptosis, but cancer cells avoid apoptosis and continue to undergo unregulated cell division. 3 While proto-oncogenes promote such cell growth and mitosis, 4 tumor suppressor genes discourage it or temporarily halt it to perform gene repair.…”

“…A class of diseases involving groups of cells displaying uncontrolled growth (proliferation), intrusion and destruction of adjacent tissues (invasion), and spreading to other parts of the body via lymph or blood (metastasis) are generally termed cancer . Damaged genes are ultimately responsible for the loss of growth control mechanisms leading to out of control cell proliferation . When cells are damaged beyond repair, they are normally eliminated by apoptosis, but cancer cells avoid apoptosis and continue to undergo unregulated cell division .…”