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Reference - PMID:19158664 - Smc5/6 maintains stalled replication forks in a recombination-competent conformation.

Reference summary

PubMed ID
PMID:19158664
Title
Smc5/6 maintains stalled replication forks in a recombination-competent conformation.
Authors
Irmisch A, Ampatzidou E, Mizuno K, O'Connell MJ, Murray JM
Citation
EMBO J 2009 Jan 21;28(2):144-55
Publication year
2009
Abstract
The Smc5/6 structural maintenance of chromosomes complex is required for efficient homologous recombination (HR). Defects in Smc5/6 result in chromosome mis-segregation and fragmentation. By characterising two Schizosaccharomyces pombe smc6 mutants, we define two separate functions for Smc5/6 in HR. The first represents the previously described defect in processing recombination-dependent DNA intermediates when replication forks collapse, which leads to increased rDNA recombination. The second novel function defines Smc5/6 as a positive regulator of recombination in the rDNA and correlates mechanistically with a requirement to load RPA and Rad52 onto chromatin genome-wide when replication forks are stably stalled by nucleotide depletion. Rad52 is required for all HR repair, but Rad52 loading in response to replication fork stalling is unexpected and does not correlate with damage-induced foci. We propose that Smc5/6 is required to maintain stalled forks in a stable recombination-competent conformation primed for replication restart.

Annotation

GO cellular component

GO:0000785 - chromatin

Genes:

Multi-locus phenotype

FYPO:0005868 - increased mitotic recombination at rDNA

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Genotypes:

FYPO:0007551 - increased protein localization to chromatin during cellular response to hydroxyurea

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FYPO:0000245 - loss of viability in stationary phase

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FYPO:0001310 - normal viability in stationary phase

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Single locus phenotype

FYPO:0000777 - abnormal double-strand break repair during vegetative growth

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Genotypes:

FYPO:0006321 - decreased protein localization to chromatin at stalled replication fork

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Genotypes:

FYPO:0005868 - increased mitotic recombination at rDNA

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FYPO:0007550 - increased number of Rad52 foci during cellular response to hydroxyurea

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Genotypes:

FYPO:0007551 - increased protein localization to chromatin during cellular response to hydroxyurea

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FYPO:0000245 - loss of viability in stationary phase

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FYPO:0005236 - normal protein localization to chromatin at stalled replication fork

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FYPO:0007552 - normal protein ubiquitination during cellular response to hydroxyurea

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FYPO:0000088 - sensitive to hydroxyurea

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