DNA Damage to a Single Chromosome End Delays Anaphase Onset

Silva, Bárbara Alcaraz; Stambaugh, Jessica R.; Yokomori, Kyoko; Shah, Jagesh V.; Berns, Michael W.

doi:10.1074/jbc.m113.535955

Cited by 20 publications

(25 citation statements)

References 74 publications

(68 reference statements)

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“…After phosphorylation and activation by Chk2, p53 induces the expression of p21, a well-known cyclin dependent kinase inhibitors (CDKI) that inactivates cyclin dependent kinase 2 (CDK2) to prevent G1/S phase progression (Jiang and Dong 2008; Miller et al 2010; Oh et al 2014; Pabla and Dong 2008; Price et al 2004a; Price et al 2009; Zannini et al 2014). Alternatively, Chk2 induces cell division cycle 25 homolog C (cdc25C) phosphorylation and translocation from nuclei to cytosol and, as a result, cdc25C can no longer activate CDK1 for G2/M phase progression and result in cell cycle arrest at G2/M (Silva et al 2014; Thomasova and Anders 2014; Zannini et al 2014). …”

Section: Dna Damage Responsementioning

confidence: 99%

DNA damage response in cisplatin-induced nephrotoxicity

et al. 2015

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Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side-effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity. In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and death, resulting in acute kidney injury (AKI). Recent studies have suggested that DNA damage and the associated DNA damage response (DDR) is an important pathogenic mechanism of AKI following cisplatin treatment. Activation of DDR may lead to cell cycle arrest and DNA repair for cell survival or, in the presence of severe injury, kidney cell death. Modulation of DDR may provide novel renoprotective strategies for cancer patients undergoing cisplatin chemotherapy.

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Section: Dna Damage Responsementioning

confidence: 99%

DNA damage response in cisplatin-induced nephrotoxicity

et al. 2015

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Section: Introductionmentioning

confidence: 84%

“…These methods of DNA damage induction result in genome-wide alterations that may lead to different DDRs. However, the laser has demonstrated to be very useful for DNA damage response studies because of its ability to target a submicron region within a specified chromosome region [23–29]. Interestingly, a laser micro-irradiation study conducted over forty years ago, showed that when the nucleolar organizer was specifically damaged in mitotic cells, a few of the irradiated cells were able to undergo a subsequent mitosis.…”

Section: Introductionmentioning

confidence: 99%

“…Studies by our lab and others have shown the ability of a diffraction-limited focused near-infrared (NIR) 780nm laser micro-beam to induce DSBs marked by γH2AX, phosphorylated Histone H2AX on Ser 139, and KU in both interphase and mitosis [29, 31–37]. In addition to γH2AX and KU at laser-damaged sites, we have demonstrated that ubiquitylation was also occurring at damage sites in mitosis [28, 29]. Though our findings differ from those that utilized ionizing radiation [5, 10], the laser micro-irradiation approach permits the visualization of proteins such as KU, that do not form ionization radiation induced foci (IRIF) [38].…”

Section: Introductionmentioning

confidence: 99%

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DNA damage induced during mitosis undergoes DNA repair synthesis

Godinez

Kabbara

Cohen

et al. 2020

Preprint

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AbstractUnderstanding 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.

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“…Using laser microirradiation, DNA damage-induced changes of the free and bound fractions of NADH were measured by FLIM in the cytoplasm and nucleus in HeLa cells. Laser microirradiation can be used to induce DNA damage in a highly controlled fashion (16,(37)(38)(39)(40).…”

Section: Phasor-approach To Flim Reveals Ratiometric Increase Of Protmentioning

confidence: 99%

NAD consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival

Murata

Kong

Moncada

et al. 2018

Preprint

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DNA damage signaling is critical for the maintenance of genome integrity and cell fate decision.Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor rapidly activated in a damage dose and complexity-dependent manner playing a critical role in the initial chromatin organization and DNA repair pathway choice at damage sites. However, the cell-wide consequence of its activation in damaged cells is not well delineated. Using the phasor approach to fluorescence lifetime imaging microscopy (FLIM) and fluorescence-based biosensors in combination with laser microirradiation, we found a rapid cell-wide increase of the bound/free NADH ratio in response to nuclear DNA damage, which is triggered by NAD+ depletion by PARP activation. This change is linked to the metabolic balance shift to oxidative phosphorylation (oxphos) over glycolysis. Inhibition of the respiratory chain resulted in rapid PARP-dependent ATP reduction and intracellular acidification, and eventually, PARPdependent, AIF-independent, apoptosis indicating that oxphos becomes critical for damaged cell survival. The results reveal the novel pro-survival effect of PARP activation through a change in cellular metabolism, and demonstrate how unique applications of advanced fluorescence imaging technologies in combination with laser microirradiation can be a powerful tool to interrogate damage-induced metabolic changes at high spatiotemporal resolution in a live cell.

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DNA Damage to a Single Chromosome End Delays Anaphase Onset

Cited by 20 publications

References 74 publications

DNA damage response in cisplatin-induced nephrotoxicity

DNA damage response in cisplatin-induced nephrotoxicity

DNA damage induced during mitosis undergoes DNA repair synthesis

NAD consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival

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