THE MITOCHONDRIAL REPLICATION INITIATOR PROTEIN UMSBP IS ESSENTIAL FOR CHROMOSOME END PROTECTION

UMS binding proteins (UMSBP) are CCHC-type zinc-finger proteins that bind the singles stranded G-rich sequence UMS, conserved at the replication origins of kinetoplast DNA, the mitochondrial genome of trypanosomatids. Here we report that Trypanosoma brucei TbUMSBP2 colocalizes with telomeres at the nuclear periphery, and is essential for telomere protection and function. Knockdown of TbUMSBP2 resulted in delocalization of the telomeres, phosphorylation of histone H2A in the vicinity of the telomeres, impaired nuclear division, endoreduplication, and cell growth arrest. Furthermore, TbUMSBP2 depletion caused rapid reduction in the G-rich telomeric overhang, and an increase in C-rich telomeric overhang and extrachromosomal telomeric circles. These results indicate that TbUMSBP2 is essential for the integrity and function of telomeres. The sequence similarity between the mitochondrial and nuclear binding targets of UMSBP proteins suggests a common function for these elements in the maintenance, segregation, and possibly coordination of replication between the two eukaryotic genomes.