Physiological functions of programmed DNA breaks in signal-induced transcription

Puc, Janusz; Aggarwal, Aneel K.; Rosenfeld, Michael G.

doi:10.1038/nrm.2017.43

Cited by 54 publications

(65 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides meiosis, PGR, and V(D)J recombination, prDSBs have been identified during signal-induced transcription in several experimental settings (see [81] for a recent review).…”

Section: Discussionmentioning

confidence: 99%

Coupling DNA Damage and Repair: an Essential Safeguard during Programmed DNA Double-Strand Breaks?

Bétermier

Borde

Villartay

2020

Trends in Cell Biology

View full text Add to dashboard Cite

DNA double strand breaks (DSBs) are the most toxic DNA lesions given their oncogenic potential. Nevertheless, programmed DSBs (prDSBs) contribute to several biological processes. Formation of prDSBs is the price to pay to achieve these essential biological functions. Generated by domesticated PiggyBac transposases, prDSBs have been integrated in the life cycle of ciliates. Created by Spo11 during meiotic recombination, they constitute a driving force of evolution and ensure balanced chromosome content for successful reproduction. Produced by the RAG1/2 recombinase, they are required for the development of the adaptive immune system in many species. The co-evolution of processes that couple introduction of prDSBs to their accurate repair may constitute an effective safeguard against genomic instability.

show abstract

“…Besides meiosis, PGR, and V(D)J recombination, prDSBs have been identified during signal-induced transcription in several experimental settings (see [81] for a recent review).…”

Section: Discussionmentioning

confidence: 99%

Coupling DNA Damage and Repair: an Essential Safeguard during Programmed DNA Double-Strand Breaks?

Bétermier

Borde

Villartay

2020

Trends in Cell Biology

View full text Add to dashboard Cite

show abstract

“…The third possible mechanism is that the apparent acute DNA damage reflects programmed single‐ and double‐strand breaks that occur to assist transcription. There is increasing evidence that topoisomerases are recruited to transcription sites where steroid hormone receptors are bound, including the glucocorticoid receptor (reviewed in Puc, Aggarwal, & Rosenfeld, 2017). These enzymes cut the DNA to ease transcription while avoiding supercoiling; following transcription, the double‐strand breaks are repaired.…”

Section: Discussionmentioning

confidence: 99%

Beyond corticosterone: The acute stress response increases DNA damage in house sparrows

et al. 2020

View full text Add to dashboard Cite

Although corticosterone (Cort) has been the predominant metric used to assess acute stress in birds, it does not always accurately reflect how an animal copes with a stressor. Downstream measurements may be more reliable. In the current study, we tested the hypothesis that acute increases in DNA damage could be used to assess stressor exposure. Studies have shown DNA damage increases in response to stress‐related hormones in vitro; however, this has not yet been thoroughly applied in wild animals. We exposed house sparrows (Passer domesticus) to a 30‐ or 120‐min restraint stressor and took blood samples at 0, 30, 60, and 120 min to measure Cort, DNA damage, and uric acid. Both treatments increased DNA damage and Cort, and decreased uric acid. It thus appears that DNA damage can reflect acute stressor exposure. To improve the usability of DNA damage as a metric for stress, we also tested the impacts of sample storage on DNA damage. Leaving red blood cells on ice for up to 24 hr, only slightly influenced DNA damage. Freezing blood samples for 1–4 weeks substantially increased DNA damage. These findings emphasize the importance of reducing variation between samples by assaying them together whenever possible. Overall, these results indicate that assessing DNA damage is a valid method of assessing acute stressor exposure that is suitable for both laboratory‐ and field‐based studies; however, additional research is needed on the molecular dynamics of nucleated red blood cells, including whether and how their DNA is repaired.

show abstract

“…However, larger number of the gH2AX signals were observed after washing in PRKDC-knockdown cells than in control cells ( Figures 1A and S1B), suggesting that the loss of DNA-PK function delays the repair of E2-induced DNA double-strand breaks. Long-lived DNA breaks (unrepaired at least 12 h after DNA damage induction) are believed to be involved in transcriptional regulation, at least in specific cases (Puc et al, 2017). To investigate the expression of ERa downstream genes under our conditions, mRNA levels were Figure 1.…”

Section: Enhancement Of Era-mediated Estrogen Signaling Causes Mammarmentioning

confidence: 99%

Estrogen Induces Mammary Ductal Dysplasia via the Upregulation of Myc Expression in a DNA-Repair-Deficient Condition

et al. 2020

View full text Add to dashboard Cite

Mammary ductal dysplasia is a phenotype observed in precancerous lesions and early-stage breast cancer. However, the mechanism of dysplasia formation remains elusive. Here we show, by establishing a novel dysplasia model system, that estrogen, a female hormone, has the potential to cause mammary ductal dysplasia. We injected estradiol (E2), the most active form of estrogen, daily into scid mice with a defect in non-homologous end joining repair and observed dysplasia formation with cell proliferation at day 30. The protooncogene Myc is a downstream target of estrogen signaling, and we found that its expression is augmented in mammary epithelial cells in this dysplasia model. Treatment with a Myc inhibitor reduced E2-induced dysplasia formation. Moreover, we found that isoflavones inhibited E2-induced dysplasia formation. Our dysplasia model system provides insights into the mechanistic understanding of breast tumorigenesis and the development of breast cancer prevention.

show abstract

Physiological functions of programmed DNA breaks in signal-induced transcription

Cited by 54 publications

References 76 publications

Coupling DNA Damage and Repair: an Essential Safeguard during Programmed DNA Double-Strand Breaks?

Coupling DNA Damage and Repair: an Essential Safeguard during Programmed DNA Double-Strand Breaks?

Beyond corticosterone: The acute stress response increases DNA damage in house sparrows

Estrogen Induces Mammary Ductal Dysplasia via the Upregulation of Myc Expression in a DNA-Repair-Deficient Condition

Contact Info

Product

Resources

About