Use your antibodies-online credentials, if available.
Despite presence of an alternative 3'-phosphatase, loss of PNKP significantly sensitizes cells to 3'-phosphate-terminated DSBs, due to a 3'-dephosphorylation defect.
PNKP mutation in two siblings is associated with progressive ataxia, abnormal saccades, sensorimotor neuropathy and dystonia consistent with ataxia with oculomotor apraxia disorders.
we have identified a mutation in PNKP, leading to a phenotype of microcephaly with primordial dwarfism.
XRCC1 (显示 XRCC1 蛋白) and PNKP interact via a high-affinity phosphorylation-dependent interaction site in XRCC1 (显示 XRCC1 蛋白) and a forkhead-associated domain in PNKP. Data suggest a second PNKP interaction site in XRCC1 (显示 XRCC1 蛋白) that binds PNKP with lower affinity and independently of XRCC1 (显示 XRCC1 蛋白) phosphorylation. (XRCC1 (显示 XRCC1 蛋白) = X-ray repair cross complementing protein 1 (显示 XRCC1 蛋白); PNKP = polynucleotide kinase 3'-phosphatase)
In a recombinant PNKP-XRCC4 (显示 XRCC4 蛋白)-LigIV complex, stable binding of PNKP requires XRCC4 (显示 XRCC4 蛋白) phosphorylation. Only one PNKP protomer binds per XRCC4 (显示 XRCC4 蛋白) dimer. Both the PNKP FHA (显示 CRY2 蛋白) and catalytic domains contact the XRCC4 (显示 XRCC4 蛋白) coiled-coil and LigIV BRCT repeats. A surface on the PNKP phosphatase domain may contact XRCC4 (显示 XRCC4 蛋白)-LigIV. A mutation on this surface (E326K) impairs PNKP recruitment to damaged DNA and causes microcephaly with seizures.
Mutations in TDP1 and APTX have been linked to Spinocerebellar ataxia with axonal neuropathy (SCAN1) and Ataxia-ocular motor apraxia 1 (AOA1), respectively, while mutations in PNKP are considered to be responsible for Microcephaly with seizures (MCSZ) and Ataxia-ocular motor apraxia 4 (AOA4).
the role for PNKP in maintaining brain function and how perturbation in its activity can account for the varied pathology of neurodegeneration or microcephaly present in microcephaly with seizures and ataxia with oculomotor apraxia 4 respectively.
In 11 Portuguese patients, PNKP mutations cause ataxia with oculomotor apraxia type 4.
Here we report that purified wild-type (WT) ATXN3 (显示 ATXN3 蛋白) stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3 (显示 ATXN3 蛋白)-deficient cells also show decreased PNKP activity
We now report that the mutant ATXN3 (显示 ATXN3 蛋白) protein interacts with and inactivates PNKP (polynucleotide kinase 3'-phosphatase), an essential DNA strand break repair enzyme
Repair independent of the well documented XRCC1 (显示 XRCC1 蛋白)-PNKP interaction was studied. XRCC1 (显示 XRCC1 蛋白) can mediate repair of strand breaks without PNKP binding.
The work indicates that the phosphatase domain of Pnkp binds 3'-phosphorylated single-stranded DNAs in a manner that is highly dependent on the presence of the 3'-phosphate.
Directed postnatal neural inactivation of PNKP affected specific subpopulations including oligodendrocytes, indicating a broad requirement for genome maintenance, both during and after neurogenesis.
Structure of dsDNA bound to PNK 5'-kinase domain reveals DNA bending facilitating recognition of DNA ends in the context of single-strand/double-strand breaks, suggesting close functional cooperation in between the kinase/phosphatase active sites.
This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.
, Homo sapiens polynucleotide kinase 3'-phosphatase (PNKP)
, bifunctional polynucleotide phosphatase/kinase
, polynucleotide kinase 3'-phosphatase
, polynucleotide kinase-3'-phosphatase