Difference between revisions of "GUARDIN"

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* Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
 
* Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
  
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===References===
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==References==
 
</references>
 
</references>
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<ref name="ref1"> Hu WL, Jin L, Xu A, Wang YF, Thorne RF, Zhang XD et al. GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability[J]. Nature cell biology. 2018, 20(4):492-502.</ref>(1)
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<ref name="ref1"> Hu WL, Jin L, Xu A, Wang YF, Thorne RF, Zhang XD et al. GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability[J]. Nature cell biology. 2018, 20(4):492-502.
 +
</ref>(1)
 
<ref name="ref2"> Georgakilas AG, Tsantoulis P, Kotsinas A, Michalopoulos I, Townsend P & Gorgoulis VG. Are common fragile sites merely structural domains or highly organized “functional” units susceptible to oncogenic stress?[J]. Cellular and molecular life sciences. 2014, 71(23):4519-4544.</ref>(2)
 
<ref name="ref2"> Georgakilas AG, Tsantoulis P, Kotsinas A, Michalopoulos I, Townsend P & Gorgoulis VG. Are common fragile sites merely structural domains or highly organized “functional” units susceptible to oncogenic stress?[J]. Cellular and molecular life sciences. 2014, 71(23):4519-4544.</ref>(2)
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<ref name="ref3"> Grossi E & Huarte M. A lncRNA GUARDINg genome integrity[J]. Nature cell biology. 2018, 20(4):371-372.</ref>(3)
+
<ref name="ref3"> Grossi E & Huarte M. A lncRNA GUARDINg genome integrity[J]. Nature cell biology. 2018, 20(4):371-372.
 +
</ref>(3)
 
</references>
 
</references>

Revision as of 08:16, 9 November 2018

lncRNA GUARDIN a p53-inducible effector which is critical for guarding the de novo structure of DNA and genomic integrity.[1]


Annotated Information

Name

GUARDIN

Alias

NA

Characteristics

GUARDIN is located between the genes encoding miR-34a and hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase (H6PD).[1] This region is part of the FRA1A(aphidicolin type, common, Fra(1)(P36)) fragile site that is frequently lost in human cancers.[2]

Function

a, Expression of the lncRNA GUARDIN is induced upon DNA damage by direct p53 transcriptional activation in order to control genome stability by multiple mechanisms. b, Thanks to several miR-23a binding sites, GUARDIN is able to sequester this miRNA and to subsequently increase expression of TRF2, an essential factor devoted to capping and protection of telomere termini. c, GUARDIN also acts as a molecular scaffold to promote the interaction between BRCA1 and its partner BARD1, thus favouring the formation of this protein complex fundamental in DNA repair. The combinatorial effect of these different GUARDIN functions leads to cell survival, antagonizing the pro-apoptotic pathway promoted by p53 following DDR.[3]

GUARDIN has a role in regulation of cell viability [1]

GUARDIN modulates the cytotoxic effect of p53 [1]

GUARDIN is necessary for preventing chromosome end-to-end fusion through maintaining the expression of telomeric repeat-binding factor 2 (TRF2) by sequestering microRNA-23a [3]

GUARDIN interacts with BRCA1 and BARD1 and is essential for the stabilization of BRCA1 [1]

GUARDIN protects genomic integrity through TRF2 and BRCA1 [1]


Regulation

GUARDIN expression is strongly induced following DNA damage.[1] GUARDIN expression is primarily regulated by wild-type p53. [1]


Diseases

GUARDIN silencing triggered apoptosis and senescence, enhanced cytotoxicity of additional genotoxic stress and inhibited cancer xenograft growth. GUARDIN may constitute a target for cancer treatment [3]


Expression

GUARDIN expression is primarily regulated by wild-type p53. However, it was detectable in TP53-null cells and in tumours with mutations in TP53, albeit at low levels.[1]


GUARDIN transcripts were concurrently reduced in a proportion of colon cancers with gene copy number loss.[1]


Labs Working

  • Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Cell and Molecular Biology, Innovation Centre for Cell Signalling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China
  • Translational Research Institute, Henan Provincial People’s Hospital, Zhengzhou, China
  • Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain

References

</references> [1](1) [2](2) [3](3)

</references>
  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Hu WL, Jin L, Xu A, Wang YF, Thorne RF, Zhang XD et al. GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability[J]. Nature cell biology. 2018, 20(4):492-502.
  2. ↑ 2.0 2.1 Georgakilas AG, Tsantoulis P, Kotsinas A, Michalopoulos I, Townsend P & Gorgoulis VG. Are common fragile sites merely structural domains or highly organized “functional” units susceptible to oncogenic stress?[J]. Cellular and molecular life sciences. 2014, 71(23):4519-4544.
  3. ↑ 3.0 3.1 3.2 3.3 Grossi E & Huarte M. A lncRNA GUARDINg genome integrity[J]. Nature cell biology. 2018, 20(4):371-372.
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