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Fanconi anemia protein FANCD2 inhibits TRF1 polyADP-ribosylation through tankyrase1-dependent manner.


ABSTRACT:

Background

Fanconi anemia (FA) is a rare autosomal recessive syndrome characterized by developmental abnormalities, progressive bone marrow failure, and predisposition to cancer. The key FA protein FANCD2 crosstalks with members of DNA damage and repair pathways that also play a role at telomeres. Therefore, we investigated whether FANCD2 has a similar involvement at telomeres.

Results

We reveal that FANCD2 may perform a novel function separate to the FANCD2/BRCA pathway. This function includes FANCD2 interaction with one of the telomere components, the PARP family member tankyrase-1. Moreover, FANCD2 inhibits tankyrase-1 activity in vitro. In turn, FANCD2 deficiency increases the polyADP-ribosylation of telomere binding factor TRF1.

Conclusions

FANCD2 binding and inhibiting tankyrase-1PARsylation at telomeres may provide an additional step within the FA pathway for the regulation of genomic integrity.

SUBMITTER: Lyakhovich A 

PROVIDER: S-EPMC3048478 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Fanconi anemia protein FANCD2 inhibits TRF1 polyADP-ribosylation through tankyrase1-dependent manner.

Lyakhovich Alex A   Lyakhovich Alex A   Ramirez Maria Jose MJ   Castellanos Andres A   Castella Maria M   Simons Amanda M AM   Parvin Jeffrey D JD   Surralles Jordi J  

Genome integrity 20110212 1


<h4>Background</h4>Fanconi anemia (FA) is a rare autosomal recessive syndrome characterized by developmental abnormalities, progressive bone marrow failure, and predisposition to cancer. The key FA protein FANCD2 crosstalks with members of DNA damage and repair pathways that also play a role at telomeres. Therefore, we investigated whether FANCD2 has a similar involvement at telomeres.<h4>Results</h4>We reveal that FANCD2 may perform a novel function separate to the FANCD2/BRCA pathway. This fun  ...[more]

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