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We have previously reported that DT40 cells deficient in the Y-family polymerase REV1 are defective in replicating G-quadruplex DNA. In vivo this leads to uncoupling of DNA synthesis from redeposition of histones displaced ahead of the replication fork, which in turn leads to loss of transcriptional repression due to failure to recycle pre-existing(More)
The past 15 years have seen an explosion in our understanding of how cells replicate damaged DNA and how this can lead to mutagenesis. The Y-family DNA polymerases lie at the heart of this process, which is commonly known as translesion synthesis. This family of polymerases has unique features that enable them to synthesize DNA past damaged bases. However,(More)
Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 micromol/L. It has been well documented that(More)
After gene rearrangement, immunoglobulin V genes are further diversified by either somatic hypermutation or gene conversion. Hypermutation (in man and mouse) occurs by the fixation of individual, non-templated nucleotide substitutions. Gene conversion (in chicken) is templated by a set of upstream V pseudogenes. Here we show that if the RAD51 paralogues(More)
The accurate propagation of histone marks during chromosomal replication is proposed to rely on the tight coupling of replication with the recycling of parental histones to the daughter strands. Here, we show in the avian cell line DT40 that REV1, a key regulator of DNA translesion synthesis at the replication fork, is required for the maintenance of(More)
Searching for an in vitro model for somatic hypermutation, we have identified an IgM-expressing Burkitt lymphoma line that constitutively diversifies its immunoglobulin V domain at high rate during culture. As in in vivo, the mutations are largely nucleotide substitutions with the pattern of substitutions revealing a component of the human hypermutation(More)
Exposure to ultraviolet light induces a number of forms of damage in DNA, of which (6-4) photoproducts present the most formidable challenge to DNA replication. No single DNA polymerase has been shown to bypass these lesions efficiently in vitro suggesting that the coordinate use of a number of different enzymes is required in vivo. To further understand(More)
The majority of DNA damage-induced mutagenesis in the yeast Saccharomyces cerevisiae arises as a result of translesion replication. This process is critically dependent on the deoxycytidyl transferase Rev1p, which forms a complex with the subunits of DNA polymerase zeta, Rev3p and Rev7p. To examine the role of Rev1 in vertebrate mutagenesis and the DNA(More)
Ubiquitination of proliferating-cell nuclear antigen (PCNA) at K164 by RAD6/RAD18 has a key role in DNA damage tolerance in yeast. Here, we report on the first genetic study of this modification in a vertebrate cell. As in yeast, mutation of K164 of PCNA to arginine in the avian cell line DT40 results in sensitivity to DNA damage but, by contrast, the DT40(More)
Monoubiquitination of FANCD2 and PCNA promotes DNA repair. It causes chromatin accumulation of FANCD2 and facilitates PCNA's recruitment of translesion polymerases to stalled replication. USP1, a protease that removes monoubiquitin from FANCD2 and PCNA, was thought to reverse the DNA damage response of these substrates. We disrupted USP1 in chicken cells to(More)