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PARP is activated at stalled forks to mediate Mre11‐dependent replication restart and recombination
Together, the data suggest that PARP1 and PARP2 detect disrupted replication forks and attract Mre11 for end processing that is required for subsequent recombination repair and restart of replication forks. Expand
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal. Expand
Stereospecific targeting of MTH1 by (S)-crizotinib as anticancer strategy
Disruption of nucleotide pool homeostasis via MTH1 inhibition by (S)-crizotinib induced an increase in DNA single-strand breaks, activated DNA repair in human colon carcinoma cells, and effectively suppressed tumour growth in animal models. Expand
Crystal structure of human MTH1 and the 8‐oxo‐dGMP product complex
MTH1 hydrolyzes oxidized nucleotide triphosphates, thereby preventing them from being incorporated into DNA. We here present the structures of human MTH1 (1.9 Å) and its complex with the productExpand
Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
A structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors suggests routes for creating isoenzyme-specific PARP inhibitors and highlights key features for potent inhibitor binding. Expand
PARP-3 Is a Mono-ADP-ribosylase That Activates PARP-1 in the Absence of DNA*
It is reported that PARP-3 small interfering RNA-depleted cells are not sensitive to the topoisomerase I poison camptothecin, inducing DNA single-strand breaks, and repair these lesions as efficiently as wild-type cells. Expand
Validation and development of MTH1 inhibitors for treatment of cancer.
It is demonstrated that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Expand
Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies
SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara -C efficacy in hematological malignancies. Expand
CyDNA: Synthesis and Replication of Highly Cy-Dye Substituted DNA by an Evolved Polymerase
In just two rounds of spCSR selection, this work has isolated a polymerase that allows the PCR amplification of double stranded DNA fragments up to 1kb, in which all dC bases are substituted by its fluorescent dye-labeled equivalent Cy3- or Cy5-dC. Expand
Processing of protein ADP-ribosylation by Nudix hydrolases.
Human Nudix (nucleoside diphosphate-linked moiety X)-type motif 16 (hNUDT16) represents a new enzyme class that can process protein ADP-ribosylation in vitro, converting it into ribose-5'-phosphate (R5P) tags covalently attached to the modified proteins. Expand