Talk:TIPIN

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Tipin was identified as a Timeless-interacting protein. Each protein depends upon the other for stability; deplete one, the other also goes away. The Timeless-Tipin complex appears to be part of a larger multi-protein complex (with AND1 and Claspin) that participates in DNA replication by coupling the DNA helicase complex that denatures duplex DNA to produce single-stranded templates to the replicative DNA polymerases that use the templates to synthesize daughter strands.<Cho WH, Kang YH, An YY, Tappin I, Hurwitz J, Lee JK. Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2523-7.> In the absence of the Timeless-Tipin complex the helicase complex may run ahead of the DNA polymerases generating excess single-stranded DNA, an unstable and risky condition, as breakage of the single-stranded DNA will generate potentially lethal DNA double strand breaks.<Smith KD, Fu MA, Brown EJ.J Cell Biol. 2009 Oct 5;187(1):15-23> Ablation of Timeless in mouse embryos was lethal and no viable pups were born, suggesting that the coupling function may be essential. The effect of Tipin knockout on embryogenesis has not been reported. It appears that Timeless may have functions independent of its interaction with Tipin operating at the level of sister chromatid cohesion through interaction with a protein complex known as cohesin.<Smith-Roe SL, Patel SS, Simpson DA, Zhou YC, Rao S, Ibrahim JG, Kaiser-Rogers KA, Cordeiro-Stone M, Kaufmann WK. Cell Cycle. 2011 May 15;10(10):1618-24.> Timeless and Tipin genes may be maximally expressed in S phase cells consistent with their role in DNA replication and establishment of sister chromatid cohesion. Enhanced Timeless gene expression has been associated with poor prognosis in several types of cancer and suggesting a role as a prognostic biomarker.<Schepeler T, Lamy P, Hvidberg V, Laurberg JR, Fristrup N, Reinert T, Bartkova J, Tropia L, Bartek J, Halazonetis TD, Pan CC, Borre M, Dyrskjøt L, Orntoft TF. Oncogene. 2013 Aug 1;32(31):3577-86. doi: 10.1038/onc.2012.381. Epub 2012 Aug 27. Williamkaufmann (talk) 14:53, 16 January 2015 (UTC)[reply]