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Evidence that DNA polymerase δ proofreads errors made by DNA polymerase α across the Saccharomyces cerevisiae nuclear genome.
DNA Repair (Amst)
November 2024
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, NC 27709, USA. Electronic address:
We show that the rates of single base substitutions, additions, and deletions across the nuclear genome are strongly increased in a strain harboring a mutator variant of DNA polymerase α combined with a mutation that inactivates the 3´-5´ exonuclease activity of DNA polymerase δ. Moreover, tetrad dissections attempting to produce a haploid triple mutant lacking Msh6, which is essential for DNA mismatch repair (MMR) of base•base mismatches made during replication, result in tiny colonies that grow very slowly and appear to be aneuploid and/or defective in oxidative metabolism. These observations are consistent with the hypothesis that during initiation of nuclear DNA replication, single-base mismatches made by naturally exonuclease-deficient DNA polymerase α are extrinsically proofread by DNA polymerase δ, such that in the absence of this proofreading, the mutation rate is strongly elevated.
View Article and Find Full Text PDFSemantic versus perceptual priming: dissecting their impact on intuitive judgments of semantic coherence.
Front Psychol
June 2024
Institute of Psychology, Polish Academy of Sciences, Warsaw, Poland.
This research explores the mechanisms underlying the intuitive processing of semantic coherence, focusing on the effects of semantic and perceptual priming on semantic coherence detection. Two studies examined how these priming types influence individuals' abilities to discern semantic incoherence. In Study 1, we used solutions to semantically coherent triads as primes, finding that such priming significantly improves participants' accuracy and confidence in identifying incoherent elements within word tetrads.
View Article and Find Full Text PDFHigh-throughput classification of S. cerevisiae tetrads using deep learning.
Yeast
July 2024
Section for Functional Genomics, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Meiotic crossovers play a vital role in proper chromosome segregation and evolution of most sexually reproducing organisms. Meiotic recombination can be visually observed in Saccharomyces cerevisiae tetrads using linked spore-autonomous fluorescent markers placed at defined intervals within the genome, which allows for analysis of meiotic segregation without the need for tetrad dissection. To automate the analysis, we developed a deep learning-based image recognition and classification pipeline for high-throughput tetrad detection and meiotic crossover classification.
View Article and Find Full Text PDFEngineered CRISPR-Cas12a for higher-order combinatorial chromatin perturbations.
Nat Biotechnol
May 2024
Department of Urology, University of California, San Francisco, CA, USA.
Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting one to three genomic sites per cell.
View Article and Find Full Text PDF[Morphological study of sexual reproductive disorders in Ligusticum chuanxiong].
Zhongguo Zhong Yao Za Zhi
March 2024
School of Pharmacy, Chengdu University of Traditional Chinese Medicine Chengdu 611137, China State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu 611137, China.
Article Synopsis
- The study employs anatomical methods to compare the reproductive growth stages of L. chuanxiong with its healthy relative, L. sinense, revealing abnormalities in pollen development for L. chuanxiong, including irregular meiosis and inactive pollen grains.
- In contrast, L. sinense exhibits normal anther development and vigorous pollen, indicating significant reproductive deficiencies in L. chuanxiong that affect its cultivation and viability.
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