AMPK-Mediated Phosphorylation on 53BP1 Promotes NHEJ

Jiang, Yuejing; Dong, Ying; Luo, Yifeng; Jiang, Shangwen; Meng, Fei-Long; Tan, Minjia; Zang, Yi; Li, Jia

doi:10.2139/ssrn.3606294

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…p97 inhibition delays DSB repair and causes a switch from ''error-free'' RAD51-mediated repair to mutagenic repair by RAD52 When ssDNA levels exceed a certain threshold, HR repair is compromised, and cells are more likely to be repaired by an alternative mutagenic end-joining pathway such as SSA (Duursma et al, 2013). Additionally, compromised 53BP1 recruitment has been shown to cause a switch from error-free gene conversion mediated by RAD51 to RAD52-mediated SSA (Ochs et al, 2016;Jiang et al, 2021). One of the mechanisms by which this occurs is through the release of an inhibitory brake on RAD52 by RAD51 (Ceccaldi et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

p97/VCP inhibition causes excessive MRE11-dependent DNA end resection promoting cell killing after ionizing radiation

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

p97/VCP inhibition causes excessive MRE11-dependent DNA end resection promoting cell killing after ionizing radiation

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Snf1 is phosphorylated during glucose deprivation by Sak1 and other kinases ( [12][13][14] and helps regulate glucose levels and the expression of genes required for metabolism of alternative sugars through a feedback loop involving a protein complex formed with the glycolytic enzyme hexokinase, Hxk2, and the transcriptional repressor, Mig1 [15,16]. Snf1 has been implicated in the DNA damage response through SUMOylation catalyzed by Mms21, a SUMO ligase [17], and its mammalian orthologue has been shown to regulate both the exonuclease Exo1 and NHEJ via the checkpoint protein 53BP1 [18,19].…”

Section: Introductionmentioning

confidence: 99%

Multiple metabolic signals including AMPK and PKA regulate glucose-stimulated double strand break resection in yeast

Lomonaco

Bazzano

Wilson

2021

Preprint

View full text Add to dashboard Cite

DNA double strand breaks (DSBs) are cytotoxic lesions repaired by non-homologous end joining (NHEJ) and homologous recombination (HR), with 5' strand resection being the committed step in transition from NHEJ to HR. We previously discovered that gal1 yeast, which cannot metabolize galactose, were unable to perform efficient 5' resection even though DSBs were formed. Adding glucose or restoring GAL1 restored resection, suggesting that carbon source metabolism signals to DSB repair. Here we demonstrate that any fermentable carbon source, including raffinose, can stimulate resection and that the stimulatory effect of glucose was associated with decreased, not increased, cellular ATP. The effect was cell cycle dependent and did not occur in G1, while glucose augmented the G2/M checkpoint arrest even in cells deficient in resection. AMP-activated protein kinase pathway mutants showed only low basal resection despite glucose addition but had normal checkpoint arrest, indicating a primary role for Snf1 specifically in glucose-stimulated resection. The metabolic inputs to resection were multifactorial, however, with loss of the transcriptional repressor Mig1 leading to increased basal resection, three distinct patterns of deficiency with loss of the protein kinase A catalytic subunits, Tpk1, Tpk2 andTpk3, and a resection delay in yeast lacking the lysine demethylase Rph1 that helped separate early and late phase responses to glucose. These results reveal multiple interrelated metabolic signals that optimize DSB resection efficiency while independently amplifying the G2/M checkpoint response.

show abstract

AMPK-Mediated Phosphorylation on 53BP1 Promotes NHEJ

Cited by 2 publications

References 0 publications

p97/VCP inhibition causes excessive MRE11-dependent DNA end resection promoting cell killing after ionizing radiation

p97/VCP inhibition causes excessive MRE11-dependent DNA end resection promoting cell killing after ionizing radiation

Multiple metabolic signals including AMPK and PKA regulate glucose-stimulated double strand break resection in yeast

Contact Info

Product

Resources

About