maintenance mechanism
Recently Published Documents


TOTAL DOCUMENTS

142
(FIVE YEARS 36)

H-INDEX

15
(FIVE YEARS 3)

2021 ◽  
Vol 119 (1) ◽  
pp. e2119258119
Author(s):  
Laura Bacete ◽  
Julia Schulz ◽  
Timo Engelsdorf ◽  
Zdenka Bartosova ◽  
Lauri Vaahtera ◽  
...  

Plant cells can be distinguished from animal cells by their cell walls and high-turgor pressure. Although changes in turgor and the stiffness of cell walls seem coordinated, we know little about the mechanism responsible for coordination. Evidence has accumulated that plants, like yeast, have a dedicated cell wall integrity maintenance mechanism. It monitors the functional integrity of the wall and maintains integrity through adaptive responses induced by cell wall damage arising during growth, development, and interactions with the environment. These adaptive responses include osmosensitive induction of phytohormone production, defense responses, as well as changes in cell wall composition and structure. Here, we investigate how the cell wall integrity maintenance mechanism coordinates changes in cell wall stiffness and turgor in Arabidopsis thaliana. We show that the production of abscisic acid (ABA), the phytohormone-modulating turgor pressure, and responses to drought depend on the presence of a functional cell wall. We find that the cell wall integrity sensor THESEUS1 modulates mechanical properties of walls, turgor loss point, ABA biosynthesis, and ABA-controlled processes. We identify RECEPTOR-LIKE PROTEIN 12 as a component of cell wall integrity maintenance–controlling, cell wall damage–induced jasmonic acid (JA) production. We propose that THE1 is responsible for coordinating changes in turgor pressure and cell wall stiffness.


2021 ◽  
Author(s):  
Michal Zimmermann ◽  
Cynthia Bernier ◽  
Beatrice Kaiser ◽  
Sara Fournier ◽  
Li Li ◽  
...  

Combinations of inhibitors of Ataxia Telangiectasia- and Rad3-related kinase (ATRi) and poly(ADP-ribose) polymerases (PARPi) synergistically kill tumor cells through modulation of complementary DNA repair pathways, but their tolerability is limited by hematological toxicities. To address this we performed a genome-wide CRISPR/Cas9 screen to identify genetic alterations that hypersensitize cells to a combination of the ATRi RP-3500 with PARPi, including deficiency in RNase H2, RAD51 paralog mutations or the Alternative Lengthening of Telomeres telomere maintenance mechanism. We show that RP-3500 and PARPi combinations kill cells carrying these genetic alterations at doses sub-therapeutic as single agents. We also demonstrate the mechanism of combination hypersensitivity in RNase H2-deficient cells, where we observe an irreversible replication catastrophe, allowing us to design a highly efficacious and tolerable in vivo dosing schedule. Altogether, we present a comprehensive dataset to inform development of ATRi and PARPi combinations and an experimental framework applicable to other drug combination strategies.


2021 ◽  
Vol 22 (20) ◽  
pp. 11101
Author(s):  
Ji-Yong Sung ◽  
Jae-Ho Cheong

Understanding the telomere maintenance mechanism (TMM) in immortal cancer cells is vital for TMM-targeted therapies in clinical settings. In this study, we classified four telomere maintenance mechanisms into telomerase, ALT, telomerase + ALT, and non-defined telomere maintenance mechanism (NDTMM) across 31 cancer types using 10,704 transcriptomic datasets from The Cancer Genome Atlas. Our results demonstrated that approximately 50% of the total cohort displayed ALT activity with high telomerase activity in most cancer types. We confirmed significant patient prognoses according to distinct TMMs in six cancer types: adrenocortical carcinoma (ACC), PAAD, HNSC, SARC, GBM, and metastatic cancer. Patients with metastasis had a poor prognosis in the ALT group (p < 0.006) subjected to RAS protein signal transduction. Glioblastoma patients had poor prognosis in NDTMM (p < 0.0043) and showed high levels of myeloid leukocyte activation. Pancreatic adenocarcinoma (p < 0.04) and head and neck squamous cell carcinoma (p < 0.046) patients had a good prognosis in the ALT group with high immune cell activation. Furthermore, we showed that master transcriptional regulators might affect the selection of the TMM pathway and explained why different telomere maintenance mechanisms exist. Furthermore, they can be used to segregate patients and predict responders to different TMM-targeted therapeutics.


2021 ◽  
Vol 2033 (1) ◽  
pp. 012100
Author(s):  
Qiongliang Chen ◽  
Xixi Pan ◽  
Xi Liu ◽  
Yongli Yi ◽  
Ce Wang

2021 ◽  
Vol 2 (3) ◽  
pp. 819-840
Author(s):  
Ayako Yamamoto ◽  
Masami Nonaka ◽  
Patrick Martineau ◽  
Akira Yamazaki ◽  
Young-Oh Kwon ◽  
...  

Abstract. Although conventionally attributed to dry dynamics, increasing evidence points to a key role of moist dynamics in the formation and maintenance of blocking events. The source of moisture crucial for these processes, however, remains elusive. In this study, we identify the moisture sources responsible for latent heating associated with the wintertime Euro-Atlantic blocking events detected over 31 years (1979–2010). To this end, we track atmospheric particles backward in time from the blocking centres for a period of 10 d using an offline Lagrangian dispersion model applied to atmospheric reanalysis data. The analysis reveals that 28 %–55 % of particles gain heat and moisture from the ocean over the course of 10 d, with higher percentages for the lower altitudes from which particles are released. Via large-scale ascent, these moist particles transport low-potential-vorticity (PV) air of low-altitude, low-latitude origins into the upper troposphere, where the amplitude of blocking is the most prominent, in agreement with previous studies. The PV of these moist particles remains significantly lower compared to their dry counterparts throughout the course of 10 d, preferentially constituting blocking cores. Further analysis reveals that approximately two-thirds of the moist particles source their moisture locally from the Atlantic, while the remaining one-third of moist particles source it from the Pacific. There is also a small fraction of moist particles that take up moisture from both the Pacific and Atlantic basins, which undergo a large-scale uplift over the Atlantic using moisture picked up over both basins. The Gulf Stream and Kuroshio and their extensions as well as the eastern Pacific northeast of Hawaii not only provide heat and moisture to moist particles but also act as “springboards” for their large-scale, cross-isentropic ascent, where its extent strongly depends on the humidity content at the time of the ascent. While the particles of Atlantic origin swiftly ascend just before their arrival at blocking, those of Pacific origin begin their ascent a few days earlier, after which they carry low-PV air in the upper troposphere while undergoing radiative cooling just as dry particles. A previous study identified a blocking maintenance mechanism, whereby low-PV air is selectively absorbed into blocking systems to prolong blocking lifetime. As they used an isentropic trajectory analysis, this mechanism was regarded as a dry process. We found that these moist particles that are fuelled over the Pacific can also act to maintain blocks in the same manner, revealing that what appears to be a blocking maintenance mechanism governed by dry dynamics alone can, in fact, be of moist origin.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1112
Author(s):  
Jesmin Akter ◽  
Takehiko Kamijo

Telomere maintenance plays important roles in genome stability and cell proliferation. Tumor cells acquire replicative immortality by activating a telomere-maintenance mechanism (TMM), either telomerase, a reverse transcriptase, or the alternative lengthening of telomeres (ALT) mechanism. Recent advances in the genetic and molecular characterization of TMM revealed that telomerase activation and ALT define distinct neuroblastoma (NB) subgroups with adverse outcomes, and represent promising therapeutic targets in high-risk neuroblastoma (HRNB), an aggressive childhood solid tumor that accounts for 15% of all pediatric-cancer deaths. Patients with HRNB frequently present with widely metastatic disease, with tumors harboring recurrent genetic aberrations (MYCN amplification, TERT rearrangements, and ATRX mutations), which are mutually exclusive and capable of promoting TMM. This review provides recent insights into our understanding of TMM in NB tumors, and highlights emerging therapeutic strategies as potential treatments for telomerase- and ALT-positive tumors.


2021 ◽  
Author(s):  
Laura Bacete ◽  
Julia Schulz ◽  
Timo Engelsdorf ◽  
Zdenka Bartosova ◽  
Lauri Vaahtera ◽  
...  

Plant cells can be distinguished from animal cells by their cell walls and high turgor pressure. Although changes in turgor and stiffness of cell walls seem coordinated, we know little about the mechanism responsible for coordination. Evidence has accumulated that plants, like yeast, have a dedicated cell wall integrity maintenance mechanism. This mechanism monitors the functional integrity of the wall and maintains it through adaptive responses when cell wall damage occurs during growth, development, and interactions with the environment. The adaptive responses include osmo-sensitive-induction of phytohormone production, defence responses as well as changes in cell wall composition and structure. Here, we investigate how the cell wall integrity maintenance mechanism coordinates changes in cell wall stiffness and turgor in Arabidopsis thaliana. We show that the production of abscisic acid (ABA), the phytohormone modulating turgor pressure and responses to drought, depends on the presence of a functional cell wall. We find that the cell wall integrity sensor THESEUS1 modulates mechanical properties of walls, turgor loss point and ABA biosynthesis. We identify RECEPTOR-LIKE PROTEIN 12 as a new component of cell wall integrity maintenance controlling cell wall damage-induced jasmonic acid production. Based on the results we propose that THE1 is responsible for coordinating changes in turgor pressure and cell wall stiffness.


2021 ◽  
Vol 351 ◽  
pp. 129284
Author(s):  
Yuhang Du ◽  
Fangwei Yang ◽  
Hang Yu ◽  
Yuliang Cheng ◽  
Yahui Guo ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document