DNA damage induced during mitosis undergoes DNA repair synthesis

Abstract

<jats:title>Abstract</jats:title><jats:p>Understanding the mitotic DNA damage response (DDR) is critical to our comprehension of cancer, premature aging and developmental disorders which are marked by DNA repair deficiencies. In this study we use a micro-focused-laser to induce DNA damage in selected mitotic chromosomes to study the subsequent repair response. Our findings demonstrate that (1) mitotic cells are capable of DNA repair as evidenced by DNA synthesis at damage sites, (2) Repair is attenuated when DNA-PKcs and ATM are simultaneously compromised, (3) Laser damage may permit the observation of previously undetected DDR proteins when damage is elicited by other methods in mitosis, and (4) Twenty five percent of mitotic DNA-damaged cells undergo a subsequent mitosis. Together these findings suggest that mitotic DDR is more complex than previously thought and may involve factors from multiple repair pathways that are better understood in interphase.</jats:p>

Laser Scissors and Tweezers to Study Chromosomes: A Review

“…Perhaps the one area where laser scissors (nanoablation) are routinely used by a significant number of labs around the world, is in the area of DNA repair. As reviewed in this article and elsewhere in this compendium of papers, a microscope-focused laser beam is used to produce either a single sub-micron damage spot on a single chromosome in mitosis and followed by studying the DNA repair process, or the focused laser is scanned through a micron-size linear track in an interphase nucleus (see cartoon depiction, Figure 11 ; Gomez-Godinez et al, 2020 ). As mentioned above, these studies have used a wide variety of lasers at different wavelength, energies, and focused spot size ( Kong et al, 2009 ).…”

“…It took almost 40 years, and the blossoming of the field of DNA repair, to demonstrate that the laser-damaged X-chromosomes likely repaired the DNA to the extent that the DNA molecule maintained its structure as one linear molecule. Surprisingly, even though the irradiated X chromosome was replicated in the clonal cells, the deletion of NOR (rDNA) was maintained ( Gomez-Godinez et al, 2020 ). This result, perhaps, explains why 21% of cells with a chromosome damaged in pro-metaphase and 37% of cells irradiated in anaphase were able to undergo subsequent cell divisions.…”

Small but strong: Mutational and functional landscapes of micronuclei in cancer genomes

“…DSBs repair and DDR machineries were once thought to be suppressed during mitosis to prevent telomere fusions 91 . However, NHEJ has found to be activated during mitosis and primarily involved in DSBs repairing 92 . Thus, more work needs to understand whether DSBs in micronucleus can activate the mitotic NHEJ pathway to facilitate the arising of chromothripsis in unincorporated micronuclei.…”

Genetic Material Manipulation and Modification by Optical Trapping and Nanosurgery-A Perspective

“…This kind of approach can have important repercussions in models of perturbed chromosomal migration, fundamental to understand cytogenetic mutations and related disorders (chromosomal abnormalities, cancer, etc.). Additionally, it has been recently highlighted the importance of the DDR activated during mitosis by the selective LS-induced damage to the chromosomes ( Gomez-Godinez et al, 2010 , 2020 ). Noteworthy, the degree of mitotic blocking/delaying depends on which mitotic stage the cell is (e.g., metaphase vs. anaphase) and what chromosome part is damaged (e.g., central vs. distal) ( Baker et al, 2010 ).…”

“…Therefore, by judiciously choosing the laser parameters (wavelength, pulse duration, power, etc.) it is possible to carry out relevant research on redox cell modulation with OT-like setups ( Westberg et al, 2016 ; Linz et al, 2016 ; Schmalz et al, 2018 ; Gomez-Godinez et al, 2020 ).…”