Histone Deacetylase Complexes Promote Trinucleotide Repeat Expansions

Genetic analysis in budding yeast and in cultured human astrocytes reveals that specific histone deacetylase complexes accelerate expansion mutations in DNA triplet repeats

New Functions of Ctf18-RFC in Preserving Genome Stability outside Its Role in Sister Chromatid Cohesion

Expansion of DNA trinucleotide repeats causes at least 15 hereditary neurological diseases, and these repeats also undergo contraction and fragility. Current models to explain this genetic instability invoke erroneous DNA repair or aberrant replication. Here we show that CAG/CTG tracts are stabilized in Saccharomyces cerevisiae by the alternative clamp loader/unloader Ctf18-Dcc1-Ctf8-RFC complex (Ctf18-RFC). Mutants in Ctf18-RFC increased all three forms of triplet repeat instability—expansions, contractions, and fragility—with effect over a wide range of allele lengths from 20–155 repeats. Ctf18-RFC predominated among the three alternative clamp loaders, with mutants in Elg1-RFC or Rad24-RFC having less effect on trinucleotide repeats. Surprisingly, chl1, scc1-73, or scc2-4 mutants defective in sister chromatid cohesion (SCC) did not increase instability, suggesting that Ctf18-RFC protects triplet repeats independently of SCC. Instead, three results suggest novel roles for Ctf18-RFC in facilitating genomic stability. First, genetic instability in mutants of Ctf18-RFC was exacerbated by simultaneous deletion of the fork stabilizer Mrc1, but suppressed by deletion of the repair protein Rad52. Second, single-cell analysis showed that mutants in Ctf18-RFC had a slowed S phase and a striking G2/M accumulation, often with an abnormal multi-budded morphology. Third, ctf18 cells exhibit increased Rad52 foci in S phase, often persisting into G2, indicative of high levels of DNA damage. The presence of a repeat tract greatly magnified the ctf18 phenotypes. Together these results indicate that Ctf18-RFC has additional important functions in preserving genome stability, besides its role in SCC, which we propose include lesion bypass by replication forks and post-replication repair

Reducing the risk of onion bacterial diseases through managing irrigation frequency and final irrigation timing

Onion bacterial diseases pose a serious economic risk to growers as they can lead to catastrophic crop losses. Moisture in the plant canopy plays a critical role in onion bacterial disease development by dispersing the pathogens onto plants (e.g., in splashing water) and keeping conditions conducive for bacterial growth. For this reason, irrigation management can be a promising avenue for controlling bacterial diseases in regions where irrigation is used widely, particularly overhead irrigation. This study investigated the effects of in-season irrigation frequency and timing of the final irrigation on onion bacterial bulb rot and marketable bulb yield over the 2020 and 2021 growing seasons in Washington State’s semi-arid Columbia Basin, using overhead irrigation. Irrigating twice as often but for shorter periods did not increase the incidence of onion bacterial diseases or affect yield compared to longer, less frequent irrigation events under the conditions of this experiment. However, timing of the final irrigation did influence bacterial disease incidence. Irrigating until the tops (leaves and necks) had fallen over on 90% of onion plants led to culling of more bulbs at harvest as a result of bacterial rot and more bulbs with bacterial rot after five months in storage compared to plots in which irrigation was stopped two weeks earlier, at 5–10% tops down. Ending irrigation at 5–10% tops down did not reduce marketable yield or affect bulb size distribution. In semi-arid regions, careful irrigation management can be an important part of managing onion bacterial diseases, particularly at the end of the season when onion plants are most vulnerable to neck and bulb infection

Pregnancy outcomes of refractory epilepsy patients treated with Brain-responsive neurostimulation.

OBJECTIVE: To study the pregnancy outcomes, including obstetric complications and fetal outcomes, in pregnant women with epilepsy (WWE) treated with direct brain-responsive neurostimulation (RNS System). METHODS: Retrospective review of obstetric outcomes and fetal outcomes in WWE treated with the RNS System at nine comprehensive epilepsy centers in the United States from 2014-2020. In addition, changes in seizure frequency, anti-seizure medications, and RNS System setting adjustments during pregnancy were investigated. RESULTS: A total of 10 subjects and 14 pregnancies were identified. The mean age at conception was 30.6 ± 4.3 years old. The mean age at implantation was 29.8 ± 4.4 years old. The mean stimulation charge densities ranged from 1.0 to 3.0 μC/cm SIGNIFICANCE: The present study is the first report of RNS System-exposed pregnancies in WWE to date. No major congenital malformations were identified. All of the obstetric complications were within the expected range of those in WWE based on previously published data. The sample size of our study is small, so accumulation of additional cases will further help depict the safety profile of treatment with the RNS System during pregnancy