Human SIRT1 and Its Affect on Homologous Recombination

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Human SIRT1 and Its Affect on Homologous Recombination

The SIRT1 gene encodes the protein Sirtuin 1. It is a member of the sirtuin family that has seven nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase members, SIRT1 – SIRT7. SIRT1 is a homolog of Sir2 gene in yeast, which is proposed by Sinclair & LaPlante (2019) to be conserved from the time of primordial lifeforms. Although Sir2 has been studied for over 35 years, and studies of mammalian SIRT1 have progressed since then, supported data on the affects of human SIRT1 have only recently begun to accumulate. SIRT1 has been found to regulate many biological systems at the molecular level including: metabolism, cancer regulation, adipose tissue creation, aging, cellular senescence, heart aging/stress, neurodegeneration, inflammation, and human cellular development and homologous recombination (Rahman & Islam, 2011; Uhl et al., 2010).

The study on SIRT1 that I chose to investigate is titled “Role of SIRT1 in homologous recombination” conducted by Uhl et al. (2010). The authors successful intent was to show that SIRT1 is  positively implicated in regulating chromosomal repair. Past data had shown that the lack of SIRT1 led to chromosomal mutations (Uhl et al., 2010) and there was data suggesting SIRT1 might actually exacerbate chromosomal instability by down-regulating the TP35 gene and Forkhead transcription factors which provide tumor protection and DNA damage repair (Uhl et al., 2010). Although I am not well-enough versed to fully understand the methods in this study, it was clearly evident that the authors systematically ruled out any variables that they knew might obfuscate the effects of the Sirtuin 1 protein on homologous recombination. This included studying the lack of Sirtuin 1 in existing human myeloid leukemia cells over time, resulting in increased chromosomal degradation when the Sirtuin family was inhibited. The net effect of this study showed that although chromosomal repair would continue without Sirtuin 1, homologous recombination was greatly enhanced when Sirtuin 1 was present. 

References

Rahman, S., & Islam, R. (2011). Mammalian Sirt1: Insights on its Biological Functions. Cell Communication & Signaling, 9(1), 11–18. https://doi.org/10.1186%2F1478-811X-9-11

Sinclair, D.A., & LaPlante, M. D. (2019). Lifespan: Why We Age―and Why We Don't Have To. Atria Books.

Uhl, M., Csernok, A., Aydin, S., Kreienberg, R., Wiesmüller, L., & Gatz, S. A. (2010). Role of SIRT1 in Homologous Recombination. DNA Repair, 9(4), 383–393. doi.org/10.1016/j.dnarep.2009.12.020

UniProt SIRT1 Entry - https://www.uniprot.org/uniprotkb/Q96EB6/entry

GneBank SIRT1 Entry - https://www.ncbi.nlm.nih.gov/gene/23411 

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