CONTROL OF CENTROMERIC LOADING OF CENP-A

Abstract

Centromere protein A (CENP-A) dictates the centromeric identity and directs the proper inheritence of genetic information from the parental cell to its progenies. The three distinct domains of CENP-A are; an unstructured amino (NH2)-terminal tail domain (NTD), a highly conserved histone fold domain, and a carboxyl (COOH) terminal tail domain. Due to the highly divergent CENP-A NH2-terminal tail, there remains a conundrum of its function. We demonstrated in Schizosaccharomyces pombe (SpCENP-A) that the complete loss of SpCENP-A NTD results in cell inviability. Exogenously expressed SpCENP-A N-terminal truncation mutants presents growth retardation and aberrant chromosomal segregation independent of ubiquitin-mediated proteolysis and heterochromatin protection. We further observed increased centromeric localisation of SpCENP-A N-terminal mutants, RNA polymerase II (RNAP II) localisation and transcription at the centromere. Our findings suggest that SpCENP-A NTD can contribute to its own centromeric loading via an RNAP II transcription mediated loading pathway.