Disease relevance of SIRT6

• SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4 weeks [1].

High impact information on SIRT6

• We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes [1].
• Genomic instability and aging-like phenotype in the absence of mammalian SIRT6 [1].
• Determination of the exon-intron splice junctions found the full-length SIRT6 protein to consist of 8 exons ranging in size from 60 bp (exon 4) to 838 bp (exon 8) [2].
• Human SIRT6 appears to be most predominantly expressed in bone cells and in the ovaries while, in the bone marrow, it is practically absent [2].
• The human Sirt6 open reading frame encodes a 355-aa protein with a predictive molecular weight of 39.1 kDa and an isoelectric point of 9.12 [2].

Biological context of SIRT6

• Here, we demonstrate that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER) [1].
• Characterization of the 5' flanking genomic region, which precedes the Sirt6 open reading frame, revealed a TATA- and CCAAT-box less promoter with an approximately 300-bp long CpG island [2].
• Fluorescence in situ hybridization analysis localized the human Sirt6 gene to chromosome 19p13.3; a region which is frequently affected by chromosomal alterations in acute leukemia [2].

Other interactions of SIRT6

• Here, two new human sirtuins (SIRT6 and SIRT7) are found to be similar to a particular subset of insect, nematode, plant, and protozoan sirtuins [3].

References