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Mutagenic Processing of Ribonucleotides in DNA by Yeast Topoisomerase I
It is demonstrated that rNMP-associated deletion formation requires the activity of Top1, a topoisomerase that relaxes supercoils by reversibly nicking duplex DNA, and the reported studies extend the role of Top 1 to include the processing of rN MPs in genomic DNA into irreversible single-strand breaks. Expand
The E box motif CAGGTG enhances somatic hypermutation without enhancing transcription.
The frequency of somatic hypermutations of an Ig kappa transgene with an artificial test insert, RS, is at least 4-fold higher than that of three related transgenes. The four transgenes differ onlyExpand
Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication.
It is found that spontaneous mutation rate is directly proportional to the transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es). Expand
Transcription as a source of genome instability
The diverse ways in which the essential process of transcription alters the underlying DNA template and thereby modifies the genetic landscape are reviewed. Expand
Role for topoisomerase 1 in transcription-associated mutagenesis in yeast
It is suggested that the accumulation of Top1 cleavage complexes is related to the level of transcription and that their removal leads to the signature deletions of transcription-associated mutagenesis in yeast. Expand
Abasic Sites in the Transcribed Strand of Yeast DNA Are Removed by Transcription-Coupled Nucleotide Excision Repair
Examining the repair of AP sites generated when uracil is removed from a highly transcribed gene in yeast demonstrates that only AP sites on the transcribed strand are efficient substrates for NER, suggesting the recruitment of the NER machinery by an AP-blocked RNA polymerase. Expand
Two distinct mechanisms of Topoisomerase 1-dependent mutagenesis in yeast.
Genetic studies confirm that there are two distinct types of hotspots associated with ribonucleoside monophosphates in DNA and suggest a novel model in which rNMP-dependent hotspots are generated by sequential Top1 reactions and are consistent with rN MP-independent hotspots reflecting processing of a trapped Top1 cleavage complex. Expand
Guanine repeat-containing sequences confer transcription-dependent instability in an orientation-specific manner in yeast.
It is demonstrated that the rate and orientation of transcription both affect the stability of Immunoglobulin switch Mu (Sμ) region sequence, and the Sμ sequence was unstable when transcription elongation was perturbed due to a defective THO complex. Expand
POLN, a Nuclear PolA Family DNA Polymerase Homologous to the DNA Cross-link Sensitivity Protein Mus308*
The identification, cloning, and characterization of POLN and its gene product, a new mammalian DNA polymerase also related to Mus308, are reported on. Expand
Different Mismatch Repair Deficiencies All Have the Same Effects on Somatic Hypermutation
It is found that both Pms2- and Mlh1-deficient mice can somatically hypermutate the Ig test gene at approximately twofold reduced frequencies, which supports the conclusion, previously reached for Msh2 mice, that MMR- deficient B cells undergoing somatic hypermutation have a short life span. Expand