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Structural highlights

Function

PIF1_HUMAN DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability. Efficiently unwinds G-quadruplex (G4) DNA structures and forked RNA-DNA hybrids. Resolves G4 structures, preventing replication pausing and double-strand breaks (DSBs) at G4 motifs. Involved in the maintenance of telomeric DNA. Inhibits telomere elongation, de novo telomere formation and telomere addition to DSBs via catalytic inhibition of telomerase. Reduces the processivity of telomerase by displacing active telomerase from DNA ends. Releases telomerase by unwinding the short telomerase RNA/telomeric DNA hybrid that is the intermediate in the telomerase reaction. Possesses an intrinsic strand annealing activity.[HAMAP-Rule:MF_03176]^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Zhang DH, Zhou B, Huang Y, Xu LX, Zhou JQ. The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity. Nucleic Acids Res. 2006 Mar 6;34(5):1393-404. Print 2006. PMID:16522649 doi:http://dx.doi.org/34/5/1393
2. ↑ Mateyak MK, Zakian VA. Human PIF helicase is cell cycle regulated and associates with telomerase. Cell Cycle. 2006 Dec;5(23):2796-804. Epub 2006 Dec 1. PMID:17172855
3. ↑ Futami K, Shimamoto A, Furuichi Y. Mitochondrial and nuclear localization of human Pif1 helicase. Biol Pharm Bull. 2007 Sep;30(9):1685-92. PMID:17827721
4. ↑ Gu Y, Masuda Y, Kamiya K. Biochemical analysis of human PIF1 helicase and functions of its N-terminal domain. Nucleic Acids Res. 2008 Nov;36(19):6295-308. doi: 10.1093/nar/gkn609. Epub 2008, Oct 3. PMID:18835853 doi:http://dx.doi.org/10.1093/nar/gkn609
5. ↑ George T, Wen Q, Griffiths R, Ganesh A, Meuth M, Sanders CM. Human Pif1 helicase unwinds synthetic DNA structures resembling stalled DNA replication forks. Nucleic Acids Res. 2009 Oct;37(19):6491-502. doi: 10.1093/nar/gkp671. Epub 2009, Aug 21. PMID:19700773 doi:http://dx.doi.org/10.1093/nar/gkp671
6. ↑ Sanders CM. Human Pif1 helicase is a G-quadruplex DNA-binding protein with G-quadruplex DNA-unwinding activity. Biochem J. 2010 Aug 15;430(1):119-28. doi: 10.1042/BJ20100612. PMID:20524933 doi:http://dx.doi.org/10.1042/BJ20100612
7. ↑ Paeschke K, Bochman ML, Garcia PD, Cejka P, Friedman KL, Kowalczykowski SC, Zakian VA. Pif1 family helicases suppress genome instability at G-quadruplex motifs. Nature. 2013 May 23;497(7450):458-62. doi: 10.1038/nature12149. Epub 2013 May 8. PMID:23657261 doi:http://dx.doi.org/10.1038/nature12149