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Journal ArticleDOI

Mechanism of eukaryotic homologous recombination.

TLDR
HR accessory factors that facilitate other stages of the Rad51- and Dmc1-catalyzed homologous DNA pairing and strand exchange reaction have also been identified.
Abstract
Homologous recombination (HR) serves to eliminate deleterious lesions, such as double-stranded breaks and interstrand crosslinks, from chromosomes. HR is also critical for the preservation of repli- cation forks, for telomere maintenance, and chromosome segrega- tion in meiosis I. As such, HR is indispensable for the maintenance of genome integrity and the avoidance of cancers in humans. The HR reaction is mediated by a conserved class of enzymes termed recombinases. Two recombinases, Rad51 and Dmc1, catalyze the pairing and shuffling of homologous DNA sequences in eukaryotic cells via a filamentous intermediate on ssDNA called the presynaptic filament. The assembly of the presynaptic filament is a rate-limiting process that is enhanced by recombination mediators, such as the breast tumor suppressor BRCA2. HR accessory factors that facil- itate other stages of the Rad51- and Dmc1-catalyzed homologous DNA pairing and strand exchange reaction have also been identified. Recent progress on elucidating the mechanisms of action of Rad51 and Dmc1 and their cohorts of ancillary factors is reviewed here.

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Citations
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Journal ArticleDOI

The DNA-damage response in human biology and disease

TL;DR: The authors' improving understanding of DNA-damage responses is providing new avenues for disease management, and these responses are biologically significant because they prevent diverse human diseases.
Journal ArticleDOI

The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway

TL;DR: Patients lacking normal NHEJ are not only sensitive to ionizing radiation (IR), but also severely immunodeficient in the range of DNA end substrate configurations upon which they can act.
Journal ArticleDOI

Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability.

TL;DR: This work surmises that CRI represents the seventh hallmark of cancer, and suggests that an additional mechanism involved in cancer-related inflammation (CRI) is induction of genetic instability by inflammatory mediators, leading to accumulation of random genetic alterations in cancer cells.
Journal ArticleDOI

Playing the End Game: DNA Double-Strand Break Repair Pathway Choice

TL;DR: Recent insights are reviewed into the mechanisms that influence the choice between competing DSB repair pathways, how this is regulated during the cell cycle, and how imbalances in this equilibrium result in genome instability.
Journal ArticleDOI

Double-Strand Break End Resection and Repair Pathway Choice

TL;DR: The components of the end resection machinery, the role of end structure, and the cell-cycle phase on resection and the interplay of end processing with NHEJ are reviewed.
References
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Journal ArticleDOI

The double-strand-break repair model for recombination

TL;DR: This work proposes a new mechanism for meiotic recombination, in which events are initiated by double-strand breaks that are enlarged to double- Strand gaps, and postmeiotic segregation can result from heteroduplex DNA formed at the boundaries of the gap-repair region.
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Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae

TL;DR: This review encompasses different aspects of DSB-induced recombination in Saccharomyces and attempts to relate genetic, molecular biological, and biochemical studies of the processes of DNA repair and recombination.
Journal ArticleDOI

Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein

TL;DR: It is suggested that the Rad51 protein, probably together with Rad52 protein, is involved in a step to convert DSBs to the next intermediate in recombination.
Journal ArticleDOI

Biallelic Inactivation of BRCA2 in Fanconi Anemia

TL;DR: It is shown that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRC a2 proteins, which may result in cancer risks similar to those observed in families withBRCA1 or BRCa2 mutations.
Journal ArticleDOI

DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression.

TL;DR: DMC1 phenotypes provide further evidence that recombination and SC formation are interrelated processes and are consistent with a requirement for DNA-DNA interactions during SC formation, and additional evidence suggests that arrest occurs at a meiosis-specific cell cycle "checkpoint" in response to a primary defect in prophase chromosome metabolism.
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