@article {125204, title = {Cellular compartmentalisation and receptor promiscuity as a strategy for accurate and robust inference of position during morphogenesis. }, journal = {Elife}, year = {2023}, month = {03/2023}, pages = {12:e79257}, abstract = {

Precise spatial patterning of cell fate during morphogenesis requires accurate inference of cellular position. In making such inferences from morphogen profiles, cells must contend with inherent stochasticity in morphogen production, transport, sensing and signalling. Motivated by the multitude of signalling mechanisms in various developmental contexts, we show how cells may utilise multiple tiers of processing (compartmentalisation) and parallel branches (multiple receptor types), together with feedback control, to bring about fidelity in morphogenetic decoding of their positions within a developing tissue. By simultaneously deploying specific and nonspecific receptors, cells achieve a more accurate and robust inference. We explore these ideas in the patterning of Drosophila melanogaster wing imaginal disc by Wingless morphogen signalling, where multiple endocytic pathways participate in decoding the morphogen gradient. The geometry of the inference landscape in the high dimensional space of parameters provides a measure for robustness and delineates stiff and sloppy directions. This distributed information processing at the scale of the cell highlights how local cell autonomous control facilitates global tissue scale design.

}, doi = {10.7554/eLife.79257}, author = {Iyer, Krishnan S and Prabhakara, C and Mayor, Satyajit and Rao, Madan} } @article {119608, title = {SMC protein RecN drives RecA filament translocation for in~vivo homology search.}, journal = {Proc Natl Acad Sci U S A}, volume = {119}, year = {2022}, month = {2022 Nov 15}, pages = {e2209304119}, abstract = {

While the molecular repertoire of the homologous recombination pathways is well studied, the search mechanism that enables recombination between distant homologous regions is poorly understood. Earlier work suggests that the recombinase RecA, an essential component for homology search, forms an elongated filament, nucleating at the break site. How this RecA structure carries out long-distance search remains unclear. Here, we follow the dynamics of RecA after induction of a single double-strand break on the chromosome. We find that the RecA-nucleoprotein filament, once formed, rapidly translocates in a directional manner in the cell, undergoing several pole-to-pole traversals, until homology search is complete. Concomitant with translocation, we observe dynamic variation in the length of the filament. Importantly in\ vivo, the RecA filament alone is incapable of such long-distance movement; both translocation and associated length variations are contingent on action of structural maintenance of chromosome (SMC)-like protein RecN, via its ATPase cycle. In summary, we have uncovered the three key elements of homology search driven by RecN: mobility of a finite segment of RecA, changes in filament length, and ability to conduct multiple pole-to-pole traversals, which together point to an optimal search strategy.

}, keywords = {Bacterial Proteins, Chromosomes, DNA, Single-Stranded, DNA-Binding Proteins, Rec A Recombinases}, issn = {1091-6490}, doi = {10.1073/pnas.2209304119}, author = {Chimthanawala, Afroze and Parmar, Jyotsana J and Kumar, Sujan and Iyer, Krishnan S and Rao, Madan and Badrinarayanan, Anjana} }