Biology subjects

Andreadis, C.

Publications and source records attributed to Andreadis, C..

3 recordsLinked to original sources

bioRxiv2023

DNA nicks in both leading and lagging strand templates can trigger break-induced replication

Encounters between replication forks and unrepaired single-strand DNA breaks (SSBs) generate single-ended double-strand breaks (seDSBs) that can later become double-ended (deDSBs) through fork convergence. seDSBs can be repaired by break-induced replication (BIR), which is a highly mutagenic pathway that is thought to be repsonsible for many of the mutations and genome rearrangements that drive cancer development. However, the frequency of BIRs deployment and its ability to be triggered by both leading and lagging template strand SSBs was unclear. Using site- and strand-specific SSBs generated by nicking enzymes, including CRISPR-Cas9n, we demonstrate that leading and lagging template strand SSBs in fission yeast are typically converted into deDSBs that are repaired primarily by error-free homologous recombination. However, both types of SSB can also trigger BIR, and the frequency of these events increases when the converging fork is delayed and the non-homologous end joining protein Ku70 is deleted.

molecular biology↗

bioRxiv2021

Ubiquitination regulates cytoophidium assembly in Schizosaccharomyces pombe

CTP synthase (CTPS), a metabolic enzyme responsible for the de novo synthesis of CTP, can form filamentous structures termed cytoophidia, which are evolutionarily conserved from bacteria to humans. Here we used Schizosaccharomyces pombe to study the cytoophidium assembly regulation by ubiquitination. We tested the CTP synthases capacity to be epigenetically modified by ubiquitin or be affected by the ubiquitination state of the cell, showed that CTPS is immunoprecipitated with ubiquitin, and that ubiquitination is important for the maintenance of the CTPS filamentous structure in fission yeast. We have identified proteins which are in complex with CTPS, including specific ubiquitination regulators which significantly affect CTPS filamentation, and mapped probable ubiquitination targets on CTPS. Furthermore, we discovered that a cohort of deubiquitinating enzymes is significant for the regulation of cytoophidium morphology. Our study provides a framework for the analysis of the effects that ubiquitination and deubiquitination have on the formation of CTPS filaments.

cell biology↗

bioRxiv2021

Transcriptomic responses of Galapagos finches to avian pox virus infection

Emerging pathogens can have devastating effects on naive hosts, but disease outcomes often vary among hosts. Comparing the cellular response of different host species to infection can provide insight into mechanisms of host defense and the basis of host susceptibility to disease. Here, we used RNA-seq to characterize the transcriptomic response of Darwins finches to avian poxvirus, which is introduced to the Galapagos Islands. We tested whether gene expression differs between infected and uninfected birds, and whether transcriptomic differences were related either to known antiviral mechanisms and/or the co-option of the host cellular environment by the virus. We compared two species, the medium ground finch (Geospiza fortis) and the vegetarian finch (Platyspiza crassirostris), to determine whether related species have similar responses to the same novel pathogen. We found that medium ground finches had a strong transcriptomic response to infection, upregulating genes involved in the innate immune response including interferon production, inflammation, and other immune signaling pathways. In contrast, vegetarian finches had a more limited response to infection. Our results also revealed evidence of viral manipulation of the hosts cellular function and metabolism, providing insight into the ways in which poxviruses affect their hosts. Many of the transcriptomic responses to infection mirrored known processes seen in model and in-vitro studies of poxviruses indicating that many pathways of host defense against poxviruses are conserved among vertebrates and present even in hosts without a long evolutionary history with the virus. At the same time, the variation we observed between closely related species indicates that some endemic species of Galapagos finch may be more susceptible to avian pox than others.

genomics↗