Abstract
Fidelity in chromosome duplication and segregation is indispensable for maintaining genomic stability and the perpetuation of life. Challenges to genome integrity jeopardize cell survival and are at the root of different types of pathologies, such as cancer. The following three main sources of genomic instability exist: DNA damage, replicative stress, and chromosome segregation defects. In response to these challenges, eukaryotic cells have evolved control mechanisms, also known as checkpoint systems, which sense under-replicated or damaged DNA and activate specialized DNA repair machineries. Cells make use of these checkpoints throughout interphase to shield genome integrity before mitosis. Later on, when the cells enter into mitosis, the spindle assembly checkpoint (SAC) is activated and remains active until the chromosomes are properly attached to the spindle apparatus to ensure an equal segregation among daughter cells. All of these processes are tightly interconnected and under strict regulation in the context of the cell division cycle. The chromosomal instability underlying cancer pathogenesis has recently emerged as a major source for understanding the mitotic processes that helps to safeguard genome integrity. Here, we review the special interconnection between the S-phase and mitosis in the presence of under-replicated DNA regions. Furthermore, we discuss what is known about the DNA damage response activated in mitosis that preserves chromosomal integrity.
Highlights
During every cell division cycle, the genome must be completely and faithfully replicated only once and correctly segregated into each new daughter cell formed in mitosis
Mitosis constitutes the final and most dramatic phase of the cell cycle, where cells orchestrate crucial changes in multiple cellular components and activate intricately signaling pathways to govern the dynamic reorganization of their cellular structure
The final goal of mitosis is the division of duplicated chromosomes resulting in two genetically identical daughter cells
Summary
During every cell division cycle, the genome must be completely and faithfully replicated only once and correctly segregated into each new daughter cell formed in mitosis. Interactions between DDR and SAC components indicate to induce repair in mitosis or protection of the damaged DNA until the cell cycle starts and it can that the ATM/ATR and SAC checkpoint pathways crosstalk to restrain mitotic progression in the be properly repaired. The following two main checkpoint mechanisms governed by apical serine/threonine kinases control replication stress and DNA damage response (DDR): ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3-related). Both of these coordinate cell cycle progression and DNA repair mechanisms to maintain genome integrity (Figure 1). During interphase, the DDR activated through these signaling kinases plays an important role in the maintenance of chromosome stability by avoiding entry into mitosis with under-replicated or damaged chromosomes
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