Wstęp

Editorial. Wstęp do 10 numeru czasopisma "Adeptus"

Damage-induced phosphorylation of Sld3 is important to block late origin firing.

Origins of replication are activated throughout the S phase of the cell cycle such that some origins fire early and others fire late to ensure that each chromosome is completely replicated in a timely fashion. However, in response to DNA damage or replication fork stalling, eukaryotic cells block activation of unfired origins. Human cells derived from patients with ataxia telangiectasia are deficient in this process due to the lack of a functional ataxia telangiectasia mutated (ATM) kinase and elicit radioresistant DNA synthesis after γ-irradiation(2). This effect is conserved in budding yeast, as yeast cells lacking the related kinase Mec1 (ATM and Rad3-related (ATR in humans)) also fail to inhibit DNA synthesis in the presence of DNA damage. This intra-S-phase checkpoint actively regulates DNA synthesis by inhibiting the firing of late replicating origins, and this inhibition requires both Mec1 and the downstream checkpoint kinase Rad53 (Chk2 in humans). However, the Rad53 substrate(s) whose phosphorylation is required to mediate this function has remained unknown. Here we show that the replication initiation protein Sld3 is phosphorylated by Rad53, and that this phosphorylation, along with phosphorylation of the Cdc7 kinase regulatory subunit Dbf4, blocks late origin firing in Saccharomyces cerevisiae. Upon exposure to DNA-damaging agents, cells expressing non-phosphorylatable alleles of SLD3 and DBF4 (SLD3-m25 and dbf4-m25, respectively) proceed through the S phase faster than wild-type cells by inappropriately firing late origins of replication. SLD3-m25 dbf4-m25 cells grow poorly in the presence of the replication inhibitor hydroxyurea and accumulate multiple Rad52 foci. Moreover, SLD3-m25 dbf4-m25 cells are delayed in recovering from transient blocks to replication and subsequently arrest at the DNA damage checkpoint. These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival

Silver Digital Content: Intergenerational Transfer of Wisdom through Seniors’ Creative Writing on the Web

The digitally wise human does not have to be a digital native as even a digital immigrant can achieve digital wisdom. For people aged 85 or more and publishing on the Web (digital sages 80+) creative writing results in social media connection and new media inclusion. However, it is mainly an expression of intergenerational transfer in which seniors’ wisdom matches digital competences of their younger cooperators. Such model of seniors’ creative writing on the Web is illustrated by action research and metaphorically named silver digital content. digital divide

F-box protein specificity for g1 cyclins is dictated by subcellular localization

Levels of G1 cyclins fluctuate in response to environmental cues and couple mitotic signaling to cell cycle entry. The G1 cyclin Cln3 is a key regulator of cell size and cell cycle entry in budding yeast. Cln3 degradation is essential for proper cell cycle control; however, the mechanisms that control Cln3 degradation are largely unknown. Here we show that two SCF ubiquitin ligases, SCF(Cdc4) and SCF(Grr1), redundantly target Cln3 for degradation. While the F-box proteins (FBPs) Cdc4 and Grr1 were previously thought to target non-overlapping sets of substrates, we find that Cdc4 and Grr1 each bind to all 3 G1 cyclins in cell extracts, yet only Cln3 is redundantly targeted in vivo, due in part to its nuclear localization. The related cyclin Cln2 is cytoplasmic and exclusively targeted by Grr1. However, Cdc4 can interact with Cdk-phosphorylated Cln2 and target it for degradation when cytoplasmic Cdc4 localization is forced in vivo. These findings suggest that Cdc4 and Grr1 may share additional redundant targets and, consistent with this possibility, grr1Delta cdc4-1 cells demonstrate a CLN3-independent synergistic growth defect. Our findings demonstrate that structurally distinct FBPs are capable of interacting with some of the same substrates; however, in vivo specificity is achieved in part by subcellular localization. Additionally, the FBPs Cdc4 and Grr1 are partially redundant for proliferation and viability, likely sharing additional redundant substrates whose degradation is important for cell cycle progression

Editorial: Towards 2030: Sustainable Development Goal 11: sustainable cities and communities; A sociological perspective

This Research Topic addresses the eleventh Sustainable Development Goal (SDG), which is to "make cities and human settlements inclusive, safe, resilient and sustainable." Several individual targets and indicators measure progress toward this goal. Researchers study, among others, urban inclusion, the influence of urban policy on socioeconomic disparities, and gentrification. This Research Topic primarily addresses the challenges and complexities of sustainable urban planning and development concerning decent work, economic growth, and associated crises due to their significant impact on urban living. The presented selection of papers was edited in collaboration with the "Frontiers in Sociology" journal and includes five articles prepared in total by ten authors from the following countries: Albania, Canada, Italy, Portugal, and the United Kingdom. Three types of articles are included: one original research article (Guerra and Sousa), two review articles (Beretta and Bracchi; Sengupta and Sengupta), and two conceptual analyses (Ciampi and Sessa; Contini and Osmanaj). This Research Topic discusses themes covering social inclusion, neighborhood development, post-pandemic development, environmental justice, green cities and communities, climate-neutral cities and communities, smart cities and communities, and smart homes

Editorial: Towards 2030: Sustainable Development Goal 1: No Poverty. A Sociological Perspective

This Research Topic focuses on the first Sustainable Development Goal (SDG) by the UN, which aims to “end poverty in all its forms everywhere.” Progress toward this goal is evaluated through various targets and indicators. The most recent SDG progress report highlighted how poverty reduction has significantly slowed and worsened, mainly due to the COVID-19 pandemic (United Nations, 2024). This unprecedented emergency has particularly affected informal workers, young people, and women. With the goal of eradicating poverty by 2030 currently off track, intensified action is crucial. Moreover, amid a growing climate crisis, significant efforts are needed to bring the 2030 targets within reach. This Research Topic examines SDG1 from a sociological perspective, focusing on its framing, geographic adaptations, stakeholder involvement, and the influence of social mobility and stratification studies, especially in the context of the challenges of the post-COVID-19 pandemic

CDC5 Inhibits the Hyperphosphorylation of the Checkpoint Kinase Rad53, Leading to Checkpoint Adaptation

The mechanistic role of the yeast kinase CDC5, in allowing cells to adapt to the presence of irreparable DNA damage and continue to divide, is revealed

Gcn5 and Sirtuins Regulate Acetylation of the Ribosomal Protein Transcription Factor Ifh1

SummaryBackgroundIn eukaryotes, ribosome biosynthesis involves the coordination of ribosomal RNA and ribosomal protein (RP) production. In S. cerevisiae, the regulation of ribosome biosynthesis occurs largely at the level of transcription. The transcription factor Ifh1 binds at RP genes and promotes their transcription when growth conditions are favorable. Although Ifh1 recruitment to RP genes has been characterized, little is known about the regulation of promoter-bound Ifh1.ResultsWe used a novel whole-cell-extract screening approach to identify Spt7, a member of the SAGA transcription complex, and the RP transactivator Ifh1 as highly acetylated nonhistone species. We report that Ifh1 is modified by acetylation specifically in an N-terminal domain. These acetylations require the Gcn5 histone acetyltransferase and are reversed by the sirtuin deacetylases Hst1 and Sir2. Ifh1 acetylation is regulated by rapamycin treatment and stress and limits the ability of Ifh1 to act as a transactivator at RP genes.ConclusionsOur data suggest a novel mechanism of regulation whereby Gcn5 functions to titrate the activity of Ifh1 following its recruitment to RP promoters to provide more than an all-or-nothing mode of transcriptional regulation. We provide insights into how the action of histone acetylation machineries converges with nutrient-sensing pathways to regulate important aspects of cell growth