PT  - JOURNAL ARTICLE
AU  - Sankaranarayanan, Sundar Ram
AU  - Polisetty, Satya Dev
AU  - Das, Kuladeep
AU  - Dumbrepatil, Arti
AU  - Medina-Pritchard, Bethan
AU  - Singleton, Martin
AU  - Jeyaprakash, A Arockia
AU  - Sanyal, Kaustuv
TI  - Functional plasticity in chromosome–microtubule coupling on the evolutionary time scale
AID  - 10.26508/lsa.202201720
DP  - 2023 Dec 01
TA  - Life Science Alliance
PG  - e202201720
VI  - 6
IP  - 12
4099  - http://www.life-science-alliance.org/content/6/12/e202201720.short
4100  - http://www.life-science-alliance.org/content/6/12/e202201720.full
SO  - Life Sci. Alliance2023 Dec 01; 6
AB  - The Dam1 complex is essential for mitotic progression across evolutionarily divergent fungi. Upon analyzing amino acid (aa) sequences of Dad2, a Dam1 complex subunit, we identified a conserved 10-aa–long Dad2 signature sequence (DSS). An arginine residue (R126) in the DSS is essential for viability in Saccharomyces cerevisiae that possesses point centromeres. The corresponding arginine residues are functionally important but not essential for viability in Candida albicans and Cryptococcus neoformans; both carry several kilobases long regional centromeres. The purified recombinant Dam1 complex containing either Dad2ΔDSS or Dad2R126A failed to bind microtubules (MTs) or form any visible rings like the WT complex. Intriguingly, functional analysis revealed that the requirement of the conserved arginine residue for chromosome biorientation and mitotic progression reduced with increasing centromere length. We propose that plasticity of the invariant arginine of Dad2 in organisms with regional centromeres is achieved by conditional elevation of the kinetochore protein(s) to enable multiple kinetochore MTs to bind to each chromosome. The capacity of a chromosome to bind multiple kinetochore MTs may mask the deleterious effects of such lethal mutations.