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The human lymphoblastoid MT1 B-cell line was previously isolated as one of a series of mutant cells able to survive the cytotoxic effects ofN-methyl-N'-nitro-N-nitrosoguanidine (MNNG single-nucleotide insertions, transversions, and A-T -k G-C transitions.In vitro assay has demonstrated that the MT1 line is in fact deficient in strand-specific correction of all eight basebase mispairs. This defect, which is manifest at or prior to the excision stage of the reaction, is due to simple deficiency of a requlred activity because MT1 nuclear extracts can be complemented by a partially purified HeLa fraction to restore in vitro repair. These findings substantiate the idea that strand-specific mismatch repair contributes to alkylation-induced cytotoxicity and imply that this process serves as a barrier to spontaneous transition, transversion, and insertion/deletion mutations in mamian cells.

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The repair of 12-, 27-, 62-, and 216-nucleotide unpaired insertion/deletion heterologies has been demonstrated in nuclear extracts of human cells. When present in covalently closed circular heteroduplexes or heteroduplexes containing a single-strand break 3 to the heterology, such structures are subject to a low level repair reaction that occurs with little strand bias. However, the presence of a single-strand break 5 to the insertion/ deletion heterology greatly increases the efficiency of rectification and directs repair to the incised DNA strand. Because nick direction of repair is independent of the strand in which a particular heterology is placed, the observed strand bias is not due to asymmetry imposed on the heteroduplex by the extrahelical DNA segment. Strand-specific repair by this system requires ATP and the four dNTPs and is inhibited by aphidicolin. Repair is independent of the mismatch repair proteins MSH2, MSH6, MLH1, and PMS2 and occurs by a mechanism that is distinct from that of the conventional mismatch repair system. Large heterology repair in nuclear extracts of human cells is also independent of the XPF gene product, and extracts of Chinese hamster ovary cells deficient in the ERCC1 and ERCC4 gene products also support the reaction.Base pairing anomalies can occur within the DNA helix as a consequence of DNA biosynthetic errors or as a result of recombinational strand transfer between sequences that differ genetically (1-4). Such pairing errors may take the form of base-base mismatches or insertion/deletion (I/D) 1 heterologies, in which one strand contains a segment of one or more unpaired nucleotides. Strand-specific correction of base-base and I/D mismatches produced during DNA biosynthesis plays an important role in mutation avoidance (2, 5, 6), and mismatch rectification within the recombination heteroduplex has been implicated in meiotic gene conversion in fungal systems (3,4,7,8).Base-base mispairs are subject to strand-specific correction by the mismatch repair systems of both prokaryotes and eukaryotes (5, 6, 9), but action of this system on I/D mismatches is limited to fairly small heterologies. The Escherichia coli mismatch repair pathway will correct I/D heterologies up to about 7 unpaired nucleotides, but larger heterologies are poorly processed by this system (10 -13). A similar specificity is characteristic of the human mismatch repair system, which can correct I/D heterologies up to about 8 unpaired nucleotides (14 -16).There is evidence, in some cases contradictory, that both prokaryotes and eukaryotes can rectify I/D heterologies with larger unpaired segments by a pathway distinct from the mismatch repair system. Using transfection assay, Dohet et al. (10) demonstrated rectification of a bacteriophage heteroduplex containing an 800-nucleotide unpaired IS1 heterology by a pathway that was independent of mutH, mutL, and mutS gene function. In contrast, Carraway and Marinus (12) failed to detect repair of large heterologies upon transformation of covalently closed circular ...

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Both craniotomy and DC were feasible treatment strategies for acute SDH. The patients with acute SDH and low GCS score treated with craniotomy or DC showed no difference in the outcomes and complications.

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The earthworm, which has stasis removal and wound-healing functions, is a widely used Chinese herbal medicine in China. Schwann cell migration is critical for the regeneration of injured nerves. Schwann cells provide an essentially supportive activity for neuron regeneration. However, the molecular migration mechanisms induced by earthworms in Schwann cells remain unclear. Here, we investigate the roles of MAPK (ERK1/2, JNK and p38) pathways for earthworm-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in Schwann cells. Moreover, earthworm induced phosphorylation of ERK1/2 and p38, but not JNK, activate the downstream signaling expression of PAs and MMPs in a time-dependent manner. Earthworm-stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with U0126 and SB203580, resulting in migration and uPA-related signal pathway inhibition. The results were confirmed using small interfering ERK1/2 and p38 RNA. These results demonstrated that earthworms can stimulate Schwann cell migration and up-regulate PAs and MMP2/9 expression mediated through the MAPK pathways, ERK1/2 and p38. Taken together, our data suggests the MAPKs (ERK1/2, p38)-, PAs (uPA, tPA)-, MMP (MMP2, MMP9) signaling pathway of Schwann cells regulated by earthworms might play a major role in Schwann cell migration and nerve regeneration.