Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Poster Abstracts

14-POS Board 14 UNRAVELING S-PHASE DYNAMICS: A UNIFIED MATHEMATICAL MODEL OF HUMAN DNA REPLICATION Chinmaya Pradhan 1 ; Nirjharini Saha 2 ; Bhakti Mehta 2 ; Mrinal Srivastava 2 ; Anupam Gupta 1 ; 1 IIT Hyderabad, Department of Physics, Hyderabad, India 2 TIFR Hyderabad, Cell Biology and Cancer Biology, Hyderabad, India A cell must progress through the four phases of the cell cycle to generate daughter cells. Among these, the S-phase plays a pivotal role in ensuring the orderly replication timing and progression of the entire genome. This phase encapsulates critical and intrinsic information about cell creation, forming the foundation of cellular identity. Here, we present a unified mathematical model of DNA replication, offering insights into at a level of detail of S-phase dynamics that will complement to experimental results. Our model explains the firing patterns of origins and fork progression across distinct genomic zones, including euchromatin, facultative heterochromatin, and constitutive heterochromatin. Additionally, it highlights how stochastic and induced-firing mechanisms cooperate to establish order in DNA replication progression within human cells. We further demonstrate how key factors like Minichromosome Maintenance loading, heterogeneous fork speed distribution, limiting factors and length of individual genomic zones constrain the dynamics of the S-phase and ultimately determine the cell’s fate. We have considered these as control parameters in our model to ensure that our model can be applicable to different types of cell lines. We have also used the model to investigate DNA replication under various mutations, Oncogenes and Drug treatments. The model’s predictions are rigorously validated against multiple experimental datasets of distinct cell lines, showcasing its robustness and accuracy.

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