We characterize the changes in chromatin structure, DNA methylation and transcription during and after homologous DNA repair (HR). We find that HR modifies the DNA methylation pattern of the repaired segment. HR also alters local histone H3 methylation as well chromatin structure by inducing DNA-chromatin loops connecting the 5' and 3' ends of the repaired gene. During a two-week period after r...

Germ line mutations in the mismatch repair (MMR) genes hMSH2 and hMLH1 account for approximately 98% of hereditary non-polyposis colorectal cancers. In addition, there is increasing evidence for an involvement of MMR gene expression in the response of cells to UV-induced skin cancer. The link between MMR and skin cancer suggests an involvement of MMR gene expression in the response of skin cell...

Drug resistance in cancer poses a major problem to the success of chemotherapy. Increased resistance to the DNA-damaging chemotherapeutic drug cisplatin may be associated with a variety of factors including decreased drug accumulation, increased intracellular levels of thiols, and increased DNA repair. We have found that mutants of the Chinese hamster ovary (CHO) and the mouse adrenocortical ca...

The RAD3 gene of Saccharomyces cerevisiae encodes an ATP-dependent 5'-3' DNA helicase, which is involved in excision repair of ultraviolet radiation damage. By hybridisation of a Schizosaccharomyces pombe genomic library with a RAD3 gene probe we have isolated the S. pombe homologue of RAD3. We have also cloned the rad15 gene of S. pombe by complementation of radiation-sensitive phenotype of th...

Extracts of Drosophila embryos and adults have been found to catalyze highly efficient DNA mismatch repair, as well as repair of 1- and 5-bp loops. For mispairs T.G and G.G, repair is nick dependent and is specific for the nicked strand of heteroduplex DNA. In contrast, repair of A.A, C.A, G.A, C.T, T.T, and C.C is not nick dependent, suggesting the presence of glycosylase activities. For nick-...

The nucleolus is a unique structural component of interphase nuclei where the ribosomal genes, trans-cribed by RNA polymerase I (RNA pol I), are organized. In the present study, the repair of UV-induced photolesions was investigated in the ribosomal DNA (rDNA) in relation to RNA pol I transcription. We used hamster cells because their repair phenotype permits the separate analysis of the major ...

Homologous recombination (HR) is essential for cellular survival in mammals. In this review, the substrates for HR, the pathways of repair, and their end products (i.e. sister chromatid exchange (SCE), gene conversion, deletions or tandem duplications) are discussed. HR is involved in the repair of DNA double-strand breaks (DSBs) and DNA lesions that occur at replication forks. A classical DSB ...