Plants prioritise water allocation to tissues that support their survival and reproduction during drought, but little is known about their tissue-specific drought tolerance mechanisms. In the case of basal buds, the extent to which they are hydraulically connected to the stem is unclear, as are their drought resistance mechanisms. To address these questions in the herbaceous annual Pisum sativum L.
View Article and Find Full Text PDFDNA damage checkpoints are key regulatory signaling cascades that arrest cell cycle progression upon DNA damage or upon DNA replication stalling and allow time for repair or correction. Failure to elicit these checkpoints can lead to genomic instability that can result in cell death or mutations, ultimately leading to diseases such as cancer. Components of the DNA damage checkpoint are attractive targets for precision medicine to treat cancers.
View Article and Find Full Text PDFBiol Rev Camb Philos Soc
June 2025
The scale and resolution of trait databases and molecular phylogenies is increasing rapidly. These resources permit many open questions in comparative biology to be addressed with the right statistical tools. Multi-response (MR) phylogenetic mixed models (PMMs) offer great potential for multivariate analyses of trait evolution.
View Article and Find Full Text PDFThe decomposition of carrion is crucial to the functioning and nutrient cycling of ecosystems, and many species use this high-quality resource. However, the availability and reliability of carrion differs across environments. Modified landscapes, such as farms and roads, often produce a high density of carcasses, with disproportionate benefits for generalist mesoscavengers that can tolerate, or are attracted to, human presence.
View Article and Find Full Text PDFThe regulation of vascular water potential (Ψ) by stomata is one of the most dynamic and important behaviours in vascular plants, playing a central role in determining gas exchange and vulnerability to drought. Yet, the species-specific characterization of Ψ regulatory behaviour in response to soil or atmospheric dryness remains elusive. We hypothesize that Ψ regulatory behaviour can only be defined when the combination of both vapour pressure deficit (VPD) and soil water potential (Ψ) effects is considered.
View Article and Find Full Text PDFMaintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central component of several crucial processes in repairing DNA and protecting genome integrity, forms filaments on DNA, which are tightly regulated. One of these RAD51 regulators is FIGNL1 (fidgetin-like 1), which prevents RAD51 genotoxic chromatin association in normal cells and persistent RAD51 foci upon DNA damage.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
April 2025
Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing and protecting genome integrity, forms filaments on DNA. RAD51 filaments are tightly regulated.
View Article and Find Full Text PDFYeast Mec1, and its mammalian ortholog, Ataxia-Telangiectasia and Rad3-related, are giant protein kinases central to replication stress and double strand DNA break repair. Mec1, in complex with Ddc2, is a 'sensor' of single stranded DNA, and phosphorylates numerous cell cycle and DNA repair factors to enforce cell cycle arrest and facilitate repair. Over the last several years, new techniques - particularly in structural biology - have provided molecular mechanisms for Mec1 function.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2023
The cell cycle checkpoint kinase Mec1 and its integral partner Ddc2 are vital for the DNA damage and replication stress response. Mec1-Ddc2 "senses" single-stranded DNA (ssDNA) by being recruited to the ssDNA binding Replication Protein A (RPA) via Ddc2. In this study, we show that a DNA damage-induced phosphorylation circuit modulates checkpoint recruitment and function.
View Article and Find Full Text PDFProc Biol Sci
October 2022
Scavenging by large carnivores is integral for ecosystem functioning by limiting the build-up of carrion and facilitating widespread energy flows. However, top carnivores have declined across the world, triggering trophic shifts within ecosystems. Here, we compare findings from previous work on predator decline against areas with recent native mammalian carnivore loss.
View Article and Find Full Text PDFThe spatial analysis of linear features (lines and curves) is a challenging and rarely attempted problem in ecology. Existing methods are typically expressed in abstract mathematical formalism, making it difficult to assess their relevance and transferability into an ecological setting. We introduce a set of concrete and accessible methods to analyze the spatial patterning of line-segment data.
View Article and Find Full Text PDFInformation-theoretic approaches to model selection, such as Akaike's information criterion (AIC) and cross validation, provide a rigorous framework to select among candidate hypotheses in ecology, yet the persistent concern of overfitting undermines the interpretation of inferred processes. A common misconception is that overfitting is due to the choice of criterion or model score, despite research demonstrating that selection uncertainty associated with score estimation is the predominant influence. Here we introduce a novel selection rule that identifies a parsimonious model by directly accounting for estimation uncertainty, while still retaining an information-theoretic interpretation.
View Article and Find Full Text PDFGlobal road networks facilitate habitat modification and are integral to human expansion. Many animals, particularly scavengers, use roads as they provide a reliable source of food, such as carrion left after vehicle collisions. Tasmania is often cited as the 'roadkill capital of Australia', with the isolated offshore islands in the Bass Strait experiencing similar, if not higher, levels of roadkill.
View Article and Find Full Text PDFGenomic stability is critical for cell survival and its effective repair when damaged is a vital process for preserving genetic information. Failure to correctly repair the genome can lead to the accumulation of mutations that ultimately drives carcinogenesis. Life has evolved sophisticated surveillance, repair pathways, and mechanisms to recognize and mend genomic lesions to preserve its integrity.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2021
In response to DNA damage or replication fork stalling, the basal activity of Mec1 is stimulated in a cell-cycle-dependent manner, leading to cell-cycle arrest and the promotion of DNA repair. Mec1 dysfunction leads to cell death in yeast and causes chromosome instability and embryonic lethality in mammals. Thus, ATR is a major target for cancer therapies in homologous recombination-deficient cancers.
View Article and Find Full Text PDFCurr Opin Struct Biol
April 2020
Homologous recombination (HR) is a faithful repair mechanism for double stranded DNA breaks. Two highly homologous master kinases, the tumour suppressors ATM and ATR (Tel1 and Mec1 in yeast), coordinate cell cycle progression with repair during HR. Despite their importance, our molecular understanding of these apical coordinators has been limited, in part due to their large sizes.
View Article and Find Full Text PDFHomologous recombination (HR) is a pathway to faithfully repair DNA double-strand breaks (DSBs). At the core of this pathway is a DNA recombinase, which, as a nucleoprotein filament on ssDNA, pairs with homologous DNA as a template to repair the damaged site. In eukaryotes Rad51 is the recombinase capable of carrying out essential steps including strand invasion, homology search on the sister chromatid and strand exchange.
View Article and Find Full Text PDFRationale: Increased expression of CLIC4 (chloride intracellular channel 4) is a feature of endothelial dysfunction in pulmonary arterial hypertension, but its role in disease pathology is not fully understood.
Objective: To identify CLIC4 effectors and evaluate strategies targeting CLIC4 signaling in pulmonary hypertension.
Methods And Results: Proteomic analysis of CLIC4-interacting proteins in human pulmonary artery endothelial cells identified regulators of endosomal trafficking, including Arf6 (ADP ribosylation factor 6) GTPase activating proteins and clathrin, while CLIC4 overexpression affected protein regulators of vesicular trafficking, lysosomal function, and inflammation.
Replication Protein A (RPA), the major eukaryotic single stranded DNA-binding protein, binds to exposed ssDNA to protect it from nucleases, participates in a myriad of nucleic acid transactions and coordinates the recruitment of other important players. RPA is a heterotrimer and coats long stretches of single-stranded DNA (ssDNA). The precise molecular architecture of the RPA subunits and its DNA binding domains (DBDs) during assembly is poorly understood.
View Article and Find Full Text PDFBiochem J
February 2017
Kindlins co-activate integrins alongside talin. They possess, like talin, a FERM domain (4.1-erythrin-radixin-moiesin domain) comprising F0-F3 subdomains, but with a pleckstrin homology (PH) domain inserted in the F2 subdomain that enables membrane association.
View Article and Find Full Text PDFActa Crystallogr F Struct Biol Commun
March 2015
The post-transcriptional addition of uridines to the 3'-end of RNAs is an important regulatory process that is critical for coding and noncoding RNA stability. In fission yeast and metazoans this untemplated 3'-uridylylation is catalysed by a single family of terminal uridylyltransferases (TUTs) whose members are adapted to specific RNA targets. In Schizosaccharomyces pombe the TUT Cid1 is responsible for the uridylylation of polyadenylated mRNAs, targeting them for destruction.
View Article and Find Full Text PDFTerminal uridylyl transferases (TUTs) are responsible for the post-transcriptional addition of uridyl residues to RNA 3' ends, leading in some cases to altered stability. The Schizosaccharomyces pombe TUT Cid1 is a model enzyme that has been characterized structurally at moderate resolution and provides insights into the larger and more complex mammalian TUTs, ZCCHC6 and ZCCHC11. Here, we report a higher resolution (1.
View Article and Find Full Text PDFKindlins are essential coactivators, with talin, of the cell surface receptors integrins and also participate in integrin outside-in signalling, and the control of gene transcription in the cell nucleus. The kindlins are ~75 kDa multidomain proteins and bind to an NPxY motif and upstream T/S cluster of the integrin β-subunit cytoplasmic tail. The hematopoietically-important kindlin isoform, kindlin-3, is critical for platelet aggregation during thrombus formation, leukocyte rolling in response to infection and inflammation and osteoclast podocyte formation in bone resorption.
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