Great leaps forward: translesion synthesis gets unstalled

Abstract

This year’s American Society of Microbiology meeting on DNA Repair and Mutagenesis * The American Society of Microbiology Meeting on DNA Repair and Mutagenesis: Mechanism, Control, and Biological Consequences; Hilton Head, SC, USA; 1–7 November 1999. Organized by Graham Walker, Errol Friedberg and Susan Wallace. *The American Society of Microbiology Meeting on DNA Repair and Mutagenesis: Mechanism, Control, and Biological Consequences; Hilton Head, SC, USA; 1–7 November 1999. Organized by Graham Walker, Errol Friedberg and Susan Wallace. was one of a series of DNA Repair meetings (held every four years) that started 25 years ago. These specialized meetings have been seminal to the development of this important field. In his opening remarks, conference co-organizer Graham Walker (Cambridge, USA) expressed concern that learning about DNA repair at this meeting would be like ‘getting a drink of water from a fire hydrant’. Walker’s analogy could not have been more apt. This exciting meeting lasted six full days, included 12 plenary sessions and four poster sessions, and was attended by almost 600 scientists. Six full days of intense scientific exchange were barely sufficient to cover the many specialized areas of DNA repair and mutagenesis, which include base-excision repair (BER), nucleotide-excision repair (NER), transcription-coupled BER and NER (TC-BER and TC-NER), translesion synthesis (TLS), mismatch repair (MMR), double-stranded-break repair, recombinational repair, and much more. This meeting report describes the highlights of a meeting that was replete with superb presentations of important, interesting and novel research (see Box 1). BOX 1 – KEY CONFERENCE RESULTS The following list identifies a few striking results presented at this year’s ASM meeting on DNA Repair and Mutagenesis, not all of which are discussed in the text. •Identification of a new superfamily of DNA polymerases specialized for replicating past DNA lesions and related to E.coli UmuC (polV) and DinB (polIV), and S. cerevisiae Rad30 (polη), Rev3 (polζ) and Rev1. •UmuC, DinB, Rad30 and Rev1 are bonafide DNA polymerases with extremely low fidelity when replicating undamaged DNA. •Human homologue of yeast Rad30 is the Xeroderma Pigmentosum Variant gene. •BER of 8-oxoG, thymine glycol and radiation damage is subject to transcription coupling in a process dependent on XPG, BRCA1, BRCA2 and BAP1. •MutL is a bona fide ATPase. •Transient mutator phenocopy can occur in yeast by temporary reduction in the level of the replicative polymerase pol δ. •Knockout mice deficient in Ung or Ogg1 do not show any change in cancer susceptibility, viability or fertility, but the Rev3 knockout mouse is nonviable. •hRad52 protein forms a seven-subunit circular structure, with seven protruding propeller-like arms, which is likely to wrap ssDNA on its surface. The following list identifies a few striking results presented at this year’s ASM meeting on DNA Repair and Mutagenesis, not all of which are discussed in the text. •Identification of a new superfamily of DNA polymerases specialized for replicating past DNA lesions and related to E.coli UmuC (polV) and DinB (polIV), and S. cerevisiae Rad30 (polη), Rev3 (polζ) and Rev1. •UmuC, DinB, Rad30 and Rev1 are bonafide DNA polymerases with extremely low fidelity when replicating undamaged DNA. •Human homologue of yeast Rad30 is the Xeroderma Pigmentosum Variant gene. •BER of 8-oxoG, thymine glycol and radiation damage is subject to transcription coupling in a process dependent on XPG, BRCA1, BRCA2 and BAP1. •MutL is a bona fide ATPase. •Transient mutator phenocopy can occur in yeast by temporary reduction in the level of the replicative polymerase pol δ. •Knockout mice deficient in Ung or Ogg1 do not show any change in cancer susceptibility, viability or fertility, but the Rev3 knockout mouse is nonviable. •hRad52 protein forms a seven-subunit circular structure, with seven protruding propeller-like arms, which is likely to wrap ssDNA on its surface.