Biology subjects

Orhan, E.

Publications and source records attributed to Orhan, E..

3 recordsLinked to original sources

bioRxiv2023

Replication poison treated BRCA1-deficient breast cancers are prone to MRE11 over-resection resulting in single strand DNA accumulation and mitotic catastrophe

BRCA1, BRCA2 and RAD51, key players of homologous recombination (HR) repair, are also involved in stalled DNA replication fork protection and repair. BRCA1-deficiency is encountered in 25% of Triple Negative Breast Cancer (TNBC). Here we investigated the sensitivity of BRCA1-deficient TNBC cell models to gemcitabine a frequently used replication poison that does not alter DNA structure. We show that BRCA1-deficient models, in contrast to their isogenic BRCA1-proficient counterparts, are superiorly sensitive to gemcitabine, accumulate massive levels of single strand DNA (ssDNA), in absence of RPA and RAD51 signals and elevated double strand break (DSB) numbers leading to cell death. Remarkably, ssDNA accumulation in gemcitabine-treated BRCA1-deficient cells was strongly diminished by the MRE11 inhibitor mirin, while it did not affect ssDNA levels resulting from PARP inhibitor olaparib treatment. The central role of MRE11 DNA resection strongly suggested that replication fork reversal may be important in response to replication poisoning by gemcitabine in BRCA1-deficient models. Furthermore, we demonstrate that gemcitabine-treated BRCA1-deficient cells showing massive ssDNA accumulation slipped into mitosis and produced mitotic bridges and micronuclei (MN) showing strong BrdU and {gamma}H2AX staining. Noticeably these BrdU-positive MN and DNA bridges triggered cGAS sensing. Our data, thus, strongly suggest that gemcitabine treatment could be beneficial in BRCA1-deficient TNBC both in terms of cancer cell death, but possibly as well in terms of antitumor immune response.

cancer biology↗

bioRxiv2020

Genome-wide association links candidate genes to fruit firmness, fruit flesh color, flowering time, and soluble solid content in apricot (Prunus armeniaca)

Apricots originated from China, Central Asia and the Near East and arrived in Anatolia, and particularly in their second homeland of Malatya province in Turkey. Apricots are outstanding summer fruits, with their beautiful attractive colour, delicious sweet taste, aroma and high vitamin and mineral content. In the current study, a total of 259 apricot genotypes from different geographical origins in Turkey were used. Significant variations were detected in fruit firmness (FF), fruit flesh color (FFC), flowering time (FT), and soluble solid content (SSC). A total of 11,532 SNPs based on DArT were developed and used in the analyses of population structure and association mapping (AM). According to the STRUCTURE (v.2.2) analysis, the apricot genotypes were divided into three groups. The mixed linear model with Q and K matrixes were used to detect the associations between the SNPs and four traits. A total of 131 SNPs were associated with FF, FFC, and SSC. The results demonstrated that AM had high potential of revealing the markers associated with economically important traits in apricot.

genomics↗

bioRxiv2018

A Diverse Range of Factors Affect the Nature of Neural Representations Underlying Short-Term Memory

Sequential and persistent activity models are two prominent models of short-term memory in neural circuits. In persistent activity models, memories are represented in persistent or nearly persistent activity patterns across a population of neurons, whereas in sequential models, memories are represented dynamically by a sequential pattern of activity across the population. Experimental evidence for both types of model in the brain has been reported previously. However, it has been unclear under what conditions these two qualitatively different types of solutions emerge in neural circuits. Here, we address this question by training recurrent neural networks on several short-term memory tasks under a wide range of circuit and task manipulations. We show that sequential and nearly persistent solutions are both part of a spectrum that emerges naturally in trained networks under different conditions. Fixed delay durations, tasks with higher temporal complexity, strong network coupling, motion-related dynamic inputs and prior training in a different task favor more sequential solutions, whereas variable delay durations, tasks with low temporal complexity, weak network coupling and symmetric Hebbian short-term synaptic plasticity favor more persistent solutions. Our results help clarify some seemingly contradictory experimental results on the existence of sequential vs. persistent activity based memory mechanisms in the brain.

neuroscience↗