Laboratory of Genome Architecture
&
DNA topology

The Centre for DNA Fingerprinting and Diagnostics (CDFD),
Hyderabad, India.

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It is fascinating to see a long thread of DNA folded into a tiny nucleus and organized to form a functional aspect of the genome. Our interest is understanding the DNA topology and 3-D genome organization in embryogenesis, cellular differentiation, and cancer progression.

Head, Laboratory of Genome Architecture

Ph.D.: University of Szeged, Szeged, Hungary.

Post Doc: IFOM Foundazione Istituto FIRC di Oncologia Moleculare, Milan, Italy

Yathish J Achar obtained his PhD from University of Szeged, Hungary, in the field of Biological sciences. As a graduate student he was involved in developing an in vitro system to study fork regression activities of several tumour suppressors including HLTF, BLM, WRN, SMARCAL1 and ZRANB3. Later, he moved to Marco Foiani laboratory in IFOM (Foundazione Istituto FIRC di Oncologia Moleculare), Milan, Italy, as a post-doctoral fellow. In IFOM he was involved in mapping DNA supercoil changes and its influence on chromatin organization using genomic approaches. He joined CDFD as a group leader in 2021.

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Open Positions

Currently, there are no open positions.

Latest Publications

Negative supercoil at gene boundaries modulates gene topology

Transcription challenges the integrity of replicating chromosomes by generating topological stress and conflicts with forks1,2. The DNA topoisomerases Top1 and Top2 and the HMGB family protein Hmo1 assist DNA replication and transcription3-6. Here we describe the topological architecture of genes in Saccharomyces cerevisiae during the G1 and S phases of the cell cycle. We found under-wound DNA at gene boundaries and over-wound DNA within coding regions. This arrangement does not depend on Pol II or S phase. Top2 and Hmo1 preserve negative supercoil at gene boundaries, while Top1 acts at coding regions. Transcription generates RNA-DNA hybrids within coding regions, independently of fork orientation. During S phase, Hmo1 protects under-wound DNA from Top2, while Top2 confines Pol II and Top1 at coding units, counteracting transcription leakage and aberrant hybrids at gene boundaries. Negative supercoil at gene boundaries prevents supercoil diffusion and nucleosome repositioning at coding regions. DNA looping occurs at Top2 clusters. We propose that Hmo1 locks gene boundaries in a cruciform conformation and, with Top2, modulates the architecture of genes that retain the memory of the topological arrangements even when transcription is repressed.