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Recombinational Repair (recombinational + repair)

Distribution by Scientific Domains

Life Sciences	80%

Selected Abstracts

Mutagenic repair of DNA interstrand crosslinks

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2010
Xi Shen
Abstract Formation of DNA interstrand crosslinks (ICLs) in chromosomal DNA imposes acute obstruction of all essential DNA functions. For over 70 years bifunctional alkylators, also known as DNA crosslinkers, have been an important class of cancer chemotherapeutic regimens. The mechanisms of ICL repair remains largely elusive. Here, we review a eukaryotic mutagenic ICL repair pathway discovered by work from several laboratories. This repair pathway, alternatively termed recombination-independent ICL repair, involves the incision activities of the nucleotide excision repair (NER) mechanism and lesion bypass polymerase(s). Repair of the ICL is initiated by dual incisions flanking the ICL on one strand of the double helix; the resulting gap is filled in by lesion bypass polymerases. The remaining lesion is subsequently removed by a second round of NER reaction. The mutagenic repair of ICL likely interacts with other cellular mechanisms such as the Fanconi anemia pathway and recombinational repair of ICLs. These aspects will also be discussed. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source]

At the birth of molecular radiation biology ,

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2001
Raymond Devoret
Abstract Rational thinking builds on feelings, too. This article starts with a tribute to Richard Setlow, an eminent scientist; it retraces as well some studies in molecular genetics that helped to understand basic questions of radiation biology. In the mid-1950s, the induction of a dormant virus (prophage) by irradiation of its host was an intriguing phenomenon. Soon, it was found that prophage induction results from the inactivation of the prophage repressor. Similarly, a score of induced cellular SOS functions were found to be induced when the LexA repressor is inactivated. Repressor inactivation involves the formation of a newly formed distinctive structure: a RecA-polymer wrapped around single-stranded DNA left by the arrest of replication at damaged sites. By touching this RecA nucleofilament, the LexA repressor is inactivated, triggering the sequential expression of SOS functions. The RecA nucleofilament acts as a chaperone, allowing recombinational repair to occur after nucleotide excision repair is over. The UmuD,C complex, synthesized slowly and parsimoniously, peaks at the end of recombinational repair, ready to be positioned at the tip of a RecA nucleofilament, placing the UmuD,C complex right at a lesion. At this location, UmuD,C prevents recombinational repair, and now acts as an error-prone paucimerase that fills the discontinuity opposite the damaged DNA. Finally, the elimination of lesions from the path of DNA polymerase, allows the resumption of DNA replication, and the SOS repair cycle switches to a normal cell cycle. Environ. Mol. Mutagen. 38:135,143, 2001. © 2001 Wiley-Liss, Inc. [source]

Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks, chromosomal instability, and reduced life span in mice

GENES, CHROMOSOMES AND CANCER, Issue 4 2003
Greg Donoho
The Brca2 tumor-suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51-interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51-interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2lex1) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2lex1 mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2lex1 mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy-terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51. © 2003 Wiley-Liss, Inc. [source]

A Resurgent Phoenix--A Hypothesis for the Origin of Meiosis

IUBMB LIFE, Issue 1 2002
Wei Li
Abstract The origin and evolution of sex is a great puzzle in biology, and meiosis is the core of sex. Here, we propose a new hypothesis that meiosis may have evolved by blending features of two responses that cells have to deal with double-strand-DNA breaks, recombinational repair and apoptosis. This hypothesis can explain some unsolved problems and is in agreement with some known molecular mechanisms, cytological phenomena, and the fossil records. Furthermore, it can predict some testable features of meiosis. [source]

Production of clastogenic DNA precursors by the nucleotide metabolism in Escherichia coli

MOLECULAR MICROBIOLOGY, Issue 1 2010
Brian Budke
Summary RdgB is a bacterial dNTPase with a strong in vitro preference for non-canonical DNA precursors dHapTP, dXTP and dITP that contain deaminated or aminogroup-modified purines. Utilization of these nucleotides by replisomes in rdgB mutants of Escherichia coli produces modified DNA, on which EndoV nicking near the base analogues initiates excision repair. Some EndoV-initiated excision events cause chromosomal fragmentation, which becomes inhibitory if recombinational repair is also inactivated (the rdgB recA co-inhibition). To reveal the sources and the identities of the non-canonical DNA precursors, intercepted by RdgB in E. coli, we characterized 17 suppressors of the rdgB recA co-inhibition. Ten suppressors affect genes of the RNA/DNA precursor metabolism, identifying the source of non-canonical DNA precursors. Comparing chromosomal fragmentation with the density of EndoV-recognized DNA modifications distinguishes three mechanisms of suppression: (i) reduction of the non-canonical dNTP production, (ii) inhibition of the base analogue excision from DNA and (iii) enhancement of the cell tolerance to chromosomal fragmentation. The suppressor analysis suggests IMP as the key intermediate in the synthesis of the clastogenic DNA precursor, most likely dITP. [source]