MTV sings jubilation for telomere biology in Drosophila

Abstract

Telomere protects the ends of linear chromosomes. Telomere dysfunction fuels genome instability that can lead to diseases such as cancer. For over 30 years, Drosophila has fascinated the field as the only major model organism that does not rely on the conserved telomerase enzyme for end protection. Instead of short DNA repeats at chromosome ends, Drosophila has domesticated retrotransposons. In addition, telomere protection can be entirely sequence-independent under normal laboratory conditions, again dissimilar to what has been established for telomerase-maintained systems. Despite these major differences, recent studies from us and others have revealed remarkable similarities between the 2 systems. In particular, with the identification of the MTV complex as an ssDNA binding complex essential for telomere integrity in Drosophila (Zhang et al. 2016 Plos Genetics), we have now established several universal principles that are intrinsic to chromosome extremities but independent of the underlying DNA sequences or the telomerase enzyme. Telomere studies in Drosophila will continue to yield fundamental insights that are instrumental to the understanding of the evolution of telomere and telomeric functions.

Keywords: CST telomere complex; drosophila telomere; epigenetic regulation; retrotransposon; ssDNA protection.

Figure 1.

A conserved parallel pathway for telomere protection. The 2 branches are centered around 2 related proteins: the ATM and the ATR checkpoint kinases. Both kinases act with their interacting proteins to control telomere integrity: ATM with the Mre11-Rad50-Nbs (MRN) complex and ATR with ATRIP. Contrary to the pathway relationship for the response to DNA damage, the downstream kinases CHK1 and CHK2 are not part of the pathway essential for telomere protection as indicated by the strikethrough.

Figure 2.

Functional similarities of capping complexes between telomerase-based and transposon-based telomere maintenance. For telomerase-maintained systems, 2 separate complexes exist that protect the dsDNA and ssDNA regions of the telomeres. For dsDNA protection, mammalian TRF2, Rap1, and yeast Taz1 and Rap1 are essential for preventing telomere fusions similar to their Drosophila counterparts of HipHop and HOAP. For ssDNA protection, the CST complex might be functionally equivalent to the newly identified MTV complex in flies.