TERT promoter mutations in telomere biology

Publication date: Available online 23 November 2016 Source:Mutation Research/Reviews in Mutation Research Author(s): Barbara Heidenreich, Rajiv Kumar Telomere repeats at chromosomal ends, critical to genome integrity, are maintained through an elaborate network of proteins and pathways. Shelterin complex proteins shield telomeres from induction of DNA damage response to overcome end protection problem. A specialized ribonucleic protein, telomerase, maintains telomere homeostasis through repeat addition to counter intrinsic shortcomings of DNA replication that leads to gradual sequence shortening in successive mitoses. The biogenesis and recruitment of telomerase composed of telomerase reverse transcriptase (TERT) subunit and an RNA component, takes place through the intricate machinery that involves an elaborate number of molecules. The synthesis of telomeres remains a controlled and limited process. Inherited mutations in the molecules involved in the process directly or indirectly cause telomeropathies. Telomerase, while present in stem cells, is deactivated due to epigenetic silencing of the rate-limiting TERT upon differentiation in most of somatic cells with a few exceptions. However, in most of the cancer cells telomerase reactivation remains a ubiquitous process and constitutes one of the major hallmarks. Discovery of mutations within the core promoter of the TERT gene that create de novo binding sites for E-twenty-six (ETS) transcription factors provided a mechani...
Source: Mutation Research Reviews in Mutation Research - Category: Genetics & Stem Cells Source Type: research