Genetics最新文献_第10页

Estimating scale-specific and localized spatial patterns in allele frequency. 估计等位基因频率的特定规模和局部空间模式。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae082

Jesse R Lasky, Margarita Takou, Diana Gamba, Timothy H Keitt

{"title":"Estimating scale-specific and localized spatial patterns in allele frequency.","authors":"Jesse R Lasky, Margarita Takou, Diana Gamba, Timothy H Keitt","doi":"10.1093/genetics/iyae082","DOIUrl":"10.1093/genetics/iyae082","url":null,"abstract":"Characterizing spatial patterns in allele frequencies is fundamental to evolutionary biology because these patterns contain evidence of underlying processes. However, the spatial scales at which gene flow, changing selection, and drift act are often unknown. Many of these processes can operate inconsistently across space, causing nonstationary patterns. We present a wavelet approach to characterize spatial pattern in allele frequency that helps solve these problems. We show how our approach can characterize spatial patterns in relatedness at multiple spatial scales, i.e. a multilocus wavelet genetic dissimilarity. We also develop wavelet tests of spatial differentiation in allele frequency and quantitative trait loci (QTL). With simulation, we illustrate these methods under different scenarios. We also apply our approach to natural populations of Arabidopsis thaliana to characterize population structure and identify locally adapted loci across scales. We find, for example, that Arabidopsis flowering time QTL show significantly elevated genetic differentiation at 300-1,300 km scales. Wavelet transforms of allele frequencies offer a flexible way to reveal geographic patterns and underlying evolutionary processes.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spontaneous and double-strand break repair-associated quasipalindrome and frameshift mutagenesis in budding yeast: role of mismatch repair. 芽殖酵母中自发和双链断裂修复相关的类核苷酸基因突变和框移突变：错配修复的作用。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae068

Neal Sugawara, Mason J Towne, Susan T Lovett, James E Haber

{"title":"Spontaneous and double-strand break repair-associated quasipalindrome and frameshift mutagenesis in budding yeast: role of mismatch repair.","authors":"Neal Sugawara, Mason J Towne, Susan T Lovett, James E Haber","doi":"10.1093/genetics/iyae068","DOIUrl":"10.1093/genetics/iyae068","url":null,"abstract":"Although gene conversion (GC) in Saccharomyces cerevisiae is the most error-free way to repair double-strand breaks (DSBs), the mutation rate during homologous recombination is 1,000 times greater than during replication. Many mutations involve dissociating a partially copied strand from its repair template and re-aligning with the same or another template, leading to -1 frameshifts in homonucleotide runs, quasipalindrome (QP)-associated mutations and microhomology-mediated interchromosomal template switches. We studied GC induced by HO endonuclease cleavage at MATα, repaired by an HMR::KI-URA3 donor. We inserted into HMR::KI-URA3 an 18-bp inverted repeat where one arm had a 4-bp insertion. Most GCs yield MAT::KI-ura3::QP + 4 (Ura-) outcomes, but template-switching produces Ura+ colonies, losing the 4-bp insertion. If the QP arm without the insertion is first encountered by repair DNA polymerase and is then (mis)used as a template, the palindrome is perfected. When the QP + 4 arm is encountered first, Ura+ derivatives only occur after second-end capture and second-strand synthesis. QP + 4 mutations are suppressed by mismatch repair (MMR) proteins Msh2, Msh3, and Mlh1, but not Msh6. Deleting Rdh54 significantly reduces QP mutations only when events creating Ura+ occur in the context of a D-loop but not during second-strand synthesis. A similar bias is found with a proofreading-defective DNA polymerase mutation (poI3-01). DSB-induced mutations differed in several genetic requirements from spontaneous events. We also created a + 1 frameshift in the donor, expanding a run of 4 Cs to 5 Cs. Again, Ura+ recombinants markedly increased by disabling MMR, suggesting that MMR acts during GC but favors the unbroken, template strand.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Illuminating the Cryptococcus neoformans species complex: unveiling intracellular structures with fluorescent-protein-based markers. 照亮新型隐球菌的物种复合体：用基于荧光蛋白的标记揭示细胞内结构。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae059

Ran Shi, Xiaorong Lin

{"title":"Illuminating the Cryptococcus neoformans species complex: unveiling intracellular structures with fluorescent-protein-based markers.","authors":"Ran Shi, Xiaorong Lin","doi":"10.1093/genetics/iyae059","DOIUrl":"10.1093/genetics/iyae059","url":null,"abstract":"Cryptococcus neoformans is a fungal pathogen of the top critical priority recognized by the World Health Organization. This clinically important fungus also serves as a eukaryotic model organism. A variety of resources have been generated to facilitate investigation of the C. neoformans species complex, including congenic pairs, well-annotated genomes, genetic editing tools, and gene deletion sets. Here, we generated a set of strains with all major organelles fluorescently marked. We tested short organelle-specific targeting sequences and successfully labeled the following organelles by fusing the targeting sequences with a fluorescence protein: the plasma membrane, the nucleus, the peroxisome, and the mitochondrion. We used native cryptococcal Golgi and late endosomal proteins fused with a fluorescent protein to label these two organelles. These fluorescence markers were verified via colocalization using organelle-specific dyes. All the constructs for the fluorescent protein tags were integrated in an intergenic safe haven region. These organelle-marked strains were examined for growth and various phenotypes. We demonstrated that these tagged strains could be employed to track cryptococcal interaction with the host in phagocytosis assays. These strains also allowed us to discover remarkable differences in the dynamics of proteins targeted to different organelles during sexual reproduction. Additionally, we revealed that \"dormant\" spores transcribed and synthesized their own proteins and trafficked the proteins to the appropriate subcellular compartments, demonstrating that spores are metabolically active. We anticipate that these newly generated fluorescent markers will greatly facilitate further investigation of cryptococcal biology and pathogenesis.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

UV damage induces production of mitochondrial DNA fragments with specific length profiles. 紫外线损伤会诱导产生具有特定长度特征的线粒体 DNA 片段。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae070

Gus Waneka, Joseph Stewart, John R Anderson, Wentao Li, Jeffrey Wilusz, Juan Lucas Argueso, Daniel B Sloan

{"title":"UV damage induces production of mitochondrial DNA fragments with specific length profiles.","authors":"Gus Waneka, Joseph Stewart, John R Anderson, Wentao Li, Jeffrey Wilusz, Juan Lucas Argueso, Daniel B Sloan","doi":"10.1093/genetics/iyae070","DOIUrl":"10.1093/genetics/iyae070","url":null,"abstract":"UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). Photodamage and other bulky lesions occurring in nuclear genomes can be repaired through nucleotide excision repair (NER), where incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current evidence suggests that the only way to eliminate bulky mtDNA damage is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with antidamage antibodies and sequenced (XR-seq) to produce high-resolution maps of active repair locations following UV exposure. We analyzed previously published datasets from Arabidopsis thaliana, Saccharomyces cerevisiae, and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with distinct secondary peaks occurring in regular intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7-8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. The mechanisms producing these fragments are unclear, but we hypothesize that they result from a previously uncharacterized DNA degradation pathway or repair mechanism in mitochondria.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clarifying Mendelian vs non-Mendelian inheritance. 澄清孟德尔遗传与非孟德尔遗传。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae078

Susan Strome, Needhi Bhalla, Rohinton Kamakaka, Upasna Sharma, William Sullivan

{"title":"Clarifying Mendelian vs non-Mendelian inheritance.","authors":"Susan Strome, Needhi Bhalla, Rohinton Kamakaka, Upasna Sharma, William Sullivan","doi":"10.1093/genetics/iyae078","DOIUrl":"10.1093/genetics/iyae078","url":null,"abstract":"Gregor Mendel developed the principles of segregation and independent assortment in the mid-1800s based on his detailed analysis of several traits in pea plants. Those principles, now called Mendel's laws, in fact, explain the behavior of genes and alleles during meiosis and are now understood to underlie \"Mendelian inheritance\" of a wide range of traits and diseases across organisms. When asked to give examples of inheritance that do NOT follow Mendel's laws, in other words, examples of non-Mendelian inheritance, students sometimes list incomplete dominance, codominance, multiple alleles, sex-linked traits, and multigene traits and cite as their sources the Khan Academy, Wikipedia, and other online sites. Against this background, the goals of this Perspective are to (1) explain to students, healthcare workers, and other stakeholders why the examples above, in fact, display Mendelian inheritance, as they obey Mendel's laws of segregation and independent assortment, even though they do not produce classic Mendelian phenotypic ratios and (2) urge individuals with an intimate knowledge of genetic principles to monitor the accuracy of learning resources and work with us and those resources to correct information that is misleading.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

siRNA that participates in Drosophila dosage compensation is produced by many 1.688X and 359 bp repeats. 参与果蝇剂量补偿的 siRNA 由许多 1.688X 和 359 bp 重复序列产生。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae074

Sudeshna Biswas, Katherine Gurdziel, Victoria H Meller

{"title":"siRNA that participates in Drosophila dosage compensation is produced by many 1.688X and 359 bp repeats.","authors":"Sudeshna Biswas, Katherine Gurdziel, Victoria H Meller","doi":"10.1093/genetics/iyae074","DOIUrl":"10.1093/genetics/iyae074","url":null,"abstract":"Organisms with differentiated sex chromosomes must accommodate unequal gene dosage in males and females. Male fruit flies increase X-linked gene expression to compensate for hemizygosity of their single X chromosome. Full compensation requires localization of the Male-Specific Lethal (MSL) complex to active genes on the male X, where it modulates chromatin to elevate expression. The mechanisms that identify X chromatin are poorly understood. The euchromatic X is enriched for AT-rich, ∼359 bp satellites termed the 1.688X repeats. Autosomal insertions of 1.688X DNA enable MSL recruitment to nearby genes. Ectopic expression of dsRNA from one of these repeats produces siRNA and partially restores X-localization of MSLs in males with defective X recognition. Surprisingly, expression of double-stranded RNA from three other 1.688X repeats failed to rescue males. We reconstructed dsRNA-expressing transgenes with sequence from two of these repeats and identified phasing of repeat DNA, rather than sequence or orientation, as the factor that determines rescue of males with defective X recognition. Small RNA sequencing revealed that siRNA was produced in flies with a transgene that rescues, but not in those carrying a transgene with the same repeat but different phasing. We demonstrate that pericentromeric X heterochromatin promotes X recognition through a maternal effect, potentially mediated by small RNA from closely related heterochromatic repeats. This suggests that the sources of siRNAs promoting X recognition are highly redundant. We propose that enrichment of satellite repeats on Drosophilid X chromosomes facilitates the rapid evolution of differentiated sex chromosomes by marking the X for compensation.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Allele frequency dynamics under sex-biased demography and sex-specific inheritance in a pedigreed jay population. 纯种松鸦种群中性别偏向人口统计和性别特异性遗传下的等位基因频率动态。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae075

Rose M H Driscoll, Felix E G Beaudry, Elissa J Cosgrove, Reed Bowman, John W Fitzpatrick, Stephan J Schoech, Nancy Chen

{"title":"Allele frequency dynamics under sex-biased demography and sex-specific inheritance in a pedigreed jay population.","authors":"Rose M H Driscoll, Felix E G Beaudry, Elissa J Cosgrove, Reed Bowman, John W Fitzpatrick, Stephan J Schoech, Nancy Chen","doi":"10.1093/genetics/iyae075","DOIUrl":"10.1093/genetics/iyae075","url":null,"abstract":"Sex-biased demography, including sex-biased survival or migration, can alter allele frequency changes across the genome. In particular, we can expect different patterns of genetic variation on autosomes and sex chromosomes due to sex-specific differences in life histories, as well as differences in effective population size, transmission modes, and the strength and mode of selection. Here, we demonstrate the role that sex differences in life history played in shaping short-term evolutionary dynamics across the genome. We used a 25-year pedigree and genomic dataset from a long-studied population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of sex-biased demography and inheritance in shaping genome-wide allele frequency trajectories. We used gene dropping simulations to estimate individual genetic contributions to future generations and to model drift and immigration on the known pedigree. We quantified differential expected genetic contributions of males and females over time, showing the impact of sex-biased dispersal in a monogamous system. Due to female-biased dispersal, more autosomal variation is introduced by female immigrants. However, due to male-biased transmission, more Z variation is introduced by male immigrants. Finally, we partitioned the proportion of variance in allele frequency change through time due to male and female contributions. Overall, most allele frequency change is due to variance in survival and births. Males and females make similar contributions to autosomal allele frequency change, but males make higher contributions to allele frequency change on the Z chromosome. Our work shows the importance of understanding sex-specific demographic processes in characterizing genome-wide allele frequency change in wild populations.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into ribosomal DNA dominance and magnification through characterization of isogenic deletion alleles. 通过等位基因缺失等位基因的表征深入了解核糖体 DNA 的优势和放大作用。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae063

Selina M Kindelay, Keith A Maggert

{"title":"Insights into ribosomal DNA dominance and magnification through characterization of isogenic deletion alleles.","authors":"Selina M Kindelay, Keith A Maggert","doi":"10.1093/genetics/iyae063","DOIUrl":"10.1093/genetics/iyae063","url":null,"abstract":"The major loci for the large primary ribosomal RNA (rRNA) genes (35S rRNAs) exist as hundreds to thousands of tandem repeats in all organisms and dozens to hundreds in Drosophila. The highly repetitive nature of the ribosomal DNA (rDNA) makes it intrinsically unstable, and many conditions arise from the reduction in or magnification of copy number, but the conditions under which it does so remain unknown. By targeted DNA damage to the rDNA of the Y chromosome, we created and investigated a series of rDNA alleles. We found that complete loss of rDNA leads to lethality after the completion of embryogenesis, blocking larval molting and metamorphosis. We find that the resident retrotransposons-R1 and R2-are regulated by active rDNA such that reduction in copy number derepresses these elements. Their expression is highest during the early first instar, when loss of rDNA is lethal. Regulation of R1 and R2 may be related to their structural arrangement within the rDNA, as we find they are clustered in the flanks of the nucleolus organizing region (NOR; the cytological appearance of the rDNA). We assessed the complex nucleolar dominance relationship between X- and Y-linked rDNA using a histone H3.3-GFP reporter construct and incorporation at the NOR and found that dominance is controlled by rDNA copy number as at high multiplicity the Y-linked array is dominant, but at low multiplicity the X-linked array becomes derepressed. Finally, we found that multiple conditions that disrupt nucleolar dominance lead to increased rDNA magnification, suggesting that the phenomena of dominance and magnification are related, and a single mechanism may underlie and unify these two longstanding observations in Drosophila.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Notch signaling without the APH-2/nicastrin subunit of gamma secretase in Caenorhabditis elegans germline stem cells. 在秀丽隐杆线虫生殖干细胞中，没有伽马分泌酶 APH-2/Nicastrin 亚基的 Notch 信号传导。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae076

David M Brinkley, Karen C Smith, Emma C Fink, Woohyun Kwen, Nina H Yoo, Zachary West, Nora L Sullivan, Alex S Farthing, Valerie A Hale, Caroline Goutte

{"title":"Notch signaling without the APH-2/nicastrin subunit of gamma secretase in Caenorhabditis elegans germline stem cells.","authors":"David M Brinkley, Karen C Smith, Emma C Fink, Woohyun Kwen, Nina H Yoo, Zachary West, Nora L Sullivan, Alex S Farthing, Valerie A Hale, Caroline Goutte","doi":"10.1093/genetics/iyae076","DOIUrl":"10.1093/genetics/iyae076","url":null,"abstract":"The final step in Notch signaling activation is the transmembrane cleavage of Notch receptor by γ secretase. Thus far, genetic and biochemical evidence indicates that four subunits are essential for γ secretase activity in vivo: presenilin (the catalytic core), APH-1, PEN-2, and APH-2/nicastrin. Although some γ secretase activity has been detected in APH-2/nicastrin-deficient mammalian cell lines, the lack of biological relevance for this activity has left the quaternary γ secretase model unchallenged. Here, we provide the first example of in vivo Notch signal transduction without APH-2/nicastrin. The surprising dispensability of APH-2/nicastrin is observed in Caenorhabditis elegans germline stem cells (GSCs) and contrasts with its essential role in previously described C. elegans Notch signaling events. Depletion of GLP-1/Notch, presenilin, APH-1, or PEN-2 causes a striking loss of GSCs. In contrast, aph-2/nicastrin mutants maintain GSCs and exhibit robust and localized expression of the downstream Notch target sygl-1. Interestingly, APH-2/nicastrin is normally expressed in GSCs and becomes essential under conditions of compromised Notch function. Further insight is provided by reconstituting the C. elegans γ secretase complex in yeast, where we find that APH-2/nicastrin increases but is not essential for γ secretase activity. Together, our results are most consistent with a revised model of γ secretase in which the APH-2/nicastrin subunit has a modulatory, rather than obligatory role. We propose that a trimeric presenilin-APH-1-PEN-2 γ secretase complex can provide a low level of γ secretase activity, and that cellular context determines whether or not APH-2/nicastrin is essential for effective Notch signal transduction.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sequence reliance of the Drosophila context-dependent transcription factor CLAMP. 果蝇上下文依赖性转录因子 CLAMP 的序列依赖性。

IF 3.3 3区生物学

Genetics Pub Date : 2024-07-08 DOI: 10.1093/genetics/iyae060

Lauren J Hodkinson, Julia Gross, Casey A Schmidt, Pamela P Diaz-Saldana, Tsutomo Aoki, Leila E Rieder

引用次数: 0