Function of cancer associated protein translin

Electronic versions

Dogfennau

Abstract

Translin and its binding partner protein Translin-associated factor-X (TRAX) have been implicated in a diverse range of cellular processes. Translin has been demonstrated to bind to both DNA and RNA and appears to be involved in the recognition of specific sequences associate with breakpoint junctions of chromosomal translocations linked with the development of some human cancers. More recently, Translin and TRAX have been found to make a heterocomplex known as C3PO which has been implicated in passenger strand removal in the RNAi pathway and tRNA processing. Translin is conserved in the fission yeast and in this study we used this facile model system to further investigate the biological function of Translin. Initial work confirmed previous findings that demonstrated loss of Translin function alone has no measureable negative affect on fission yeast cells. However, we addressed the hypothesis that Translin functioned in a redundant pathway with the RNAi pathway component Dicer and found that when Dicer and Translin are disrupted there are enhanced levels of genome instability which are not due to failures in the DNA damage response. Further investigation demonstrated that this was due to an enhanced failure in the function of centromeric heterochromatin, which is regulated in part by the RNAi pathway. Here we present a model demonstrating that Translin is the key regulator of a previously inferred argonaute-dependent, Dicer-independent regulator of centromeric heterochromatin function and chromosome stability.

Details

Iaith wreiddiolSaesneg
Goruchwylydd / Goruchwylwyr / Cynghorydd
    Dyddiad dyfarnuIon 2012