SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair
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SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair
Breaking and sealing one strand of DNA is an inherent feature of chromosome metabolism to overcome torsional barriers. Failure to reseal broken DNA strands results in protein-linked DNA breaks, causing neurodegeneration in humans. This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1), which removes stalled topoisomerase 1 peptides from DNA termini. Here we show that TDP1 is a su...
متن کاملTDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo.
Defective Tyrosyl-DNA phosphodiesterase 1 (TDP1) can cause spinocerebellar ataxia with axonal neuropathy (SCAN1), a neurodegenerative syndrome associated with marked cerebellar atrophy and peripheral neuropathy. Although SCAN1 lymphoblastoid cells show pronounced defects in the repair of chromosomal single-strand breaks (SSBs), it is unknown if this DNA repair activity is important for neurons ...
متن کاملTDP1-dependent DNA single-strand break repair and neurodegeneration.
DNA single-strand breaks (SSBs) are the commonest DNA lesions that arise spontaneously in living cells. Cells employ efficient processes for the rapid repair of these breaks and defects in these processes appear to preferentially impact on the nervous system, causing human ataxia. Spinocerebellar ataxia with axonal neuropathy (SCAN1) is a human disease that is associated with a defect in repair...
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CK2 was the first protein kinase identified and is required for the proliferation and survival of mammalian cells. Here, we have identified an unanticipated role for CK2. We show that this essential protein kinase phosphorylates the scaffold protein XRCC1 and thereby enables the assembly and activity of DNA single-strand break repair protein complexes in vitro and at sites of chromosomal breaka...
متن کاملTDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks.
Tyrosyl DNA phosphodiesterase-1 (TDP1) is the gene product mutated in spinocerebellar ataxia with axonal neuropathy1 (SCAN1). SCAN1 is a hereditary ataxia that lacks extra-neurological phenotype, pointing to a critical role for TDP1 in the nervous system. Recently, we showed that TDP1 is associated with the DNA single-strand break (SSBR) repair machinery through an interaction with DNA ligase 3...
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ژورنال
عنوان ژورنال: Nature Communications
سال: 2012
ISSN: 2041-1723
DOI: 10.1038/ncomms1739