Biology subjects

Zahraeifard, S.

Publications and source records attributed to Zahraeifard, S..

2 recordsLinked to original sources

bioRxiv2026

Comprehensive Analysis Reveals Adaptive DNA Repair and Replication Stress Networks in Genomically Unstable Breast Cancer

Genomic instability is a defining hallmark of breast cancer, yet the mechanisms by which tumors tolerate persistent DNA damage remain poorly understood. We performed a comprehensive, multi-cohort analysis of breast cancer datasets to define how DNA damage response (DDR) and replication stress tolerance (RST) networks are rewired in genomically unstable tumors. Using fraction of genome altered (FGA) as a chromosomal instability metric, we show that BRCA-mutant tumors exhibit elevated genomic instability coupled with increased expression of homologous recombination, Fanconi anemia, mismatch repair, base excision repair, and alternative end-joining pathways. Strikingly, heightened pathway activity correlates with increased genome alteration, supporting a model of damage tolerance rather than repair restoration. RST programs, including fork remodeling, protection, and single strand DNA gap suppression, further contribute to tumor fitness under replication stress. These adaptive states are enriched in aggressive subtypes, intensified with progression, and associate with pathway-specific mutational burden. Co-occurrence and mutual exclusivity mapping uncovered non-random subtype-relevant genetic interactions states among major drivers and DDR genes, nominating context-specific synthetic lethal opportunities. Our findings identify compensatory genome-maintenance programs as central drivers of tumor resilience and highlight pathway-specific vulnerabilities for targeted therapeutic intervention.

cancer biology↗

bioRxiv2019

Defining chromatin state transitions predicts a network that modulates cell wall remodeling in phosphate-starved rice shoots

Phosphorus (P) is an essential plant macronutrient vital to fundamental metabolic processes. Plant-available P is low in most soils, making it a frequent limiter of growth. Declining P reserves for fertilizer production exasperates this agricultural challenge. Plants modulate complex responses to fluctuating P levels via global transcriptional regulatory networks. Although chromatin structure plays a substantial role in controlling gene expression, the chromatin dynamics involved in regulating P homeostasis have not been determined. Here we define distinct chromatin states across the rice genome by integrating multiple aspects of chromatin structure, including the H2A.Z histone variant, H3K4me3 modification, and nucleosome positioning. In response to P starvation, 40% of all protein-coding genes exhibit a transition from one chromatin state to another at their transcription start site. Several of these transitions are enriched in subsets of genes differentially expressed by P deficiency. The most prominent subset supports the presence of a coordinated signaling network that targets cell wall structure and is regulated in part via a decrease of H3K4me3 at the transcription start site. The P-starvation induced chromatin dynamics and correlated genes identified here will aid in enhancing P-use efficiency in crop plants, benefitting global agriculture.\n\nOne sentence summaryCombining data for three components of chromatin structure from control and phosphate-starved rice shoots reveals specific chromatin state transitions that correlate with subsets of functionally distinct differentially-expressed genes.

plant biology↗