Alladi Ramakrishnan Hall

Replication Forks & Chromosome Territories: Signaling mechanisms during their repairs

Prof. B.J. Rao

Department of Biological Sciences, TIFR, Mumbai

Chromosomes are functionally dynamic entities. They exhibit non-random spatial distribution that reversibly change during DNA Damage Response. A signalling cascade initiated by ATM apical kinase marks DNA damaged chromatin foci whose remodelling is innately associated with spatial changes in chromosomes. Thus the microscopic changes (chromatin foci) are causally connected to macroscopic changes in the genome (spatial movements of chromosomes). We discovered that nuclear myosin recruitment to chromosomes makes this connect. The intricate details of such a cross-talk are still unknown. Replication Forks are other examples of microscopic functional zones in chromosomes that operate locally, but impact chromosomal dynamics globally. Replication Fork stress leads to elaborate protective mechanisms involving ATR as well as ATM apical kinase responses. I describe differential roles of ATR versus ATM signalling in Replication Fork repair and the associated spatial changes in chromosomes.