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Reference - PMID:31563844 - The roles of fission yeast exonuclease 5 in nuclear and mitochondrial genome stability.

Reference summary

PubMed ID
PMID:31563844
Title
The roles of fission yeast exonuclease 5 in nuclear and mitochondrial genome stability.
Authors
Sparks JL, Gerik KJ, Stith CM, Yoder BL, Burgers PM
Citation
DNA Repair (Amst) 2019 Nov;83:102720
Publication year
2019
Abstract
The Exo5 family consists of bi-directional, single-stranded DNA-specific exonucleases that contain an iron-sulfur cluster as a structural motif and have multiple roles in DNA metabolism. S. cerevisiae Exo5 is essential for mitochondrial genome maintenance, while the human ortholog is important for nuclear genome stability and DNA repair. Here, we identify the Exo5 ortholog in Schizosaccharomyes pombe (spExo5). The activity of spExo5 is highly similar to that of the human enzyme. When the single-stranded DNA is coated with single-stranded DNA binding protein RPA, spExo5 become a 5'-specific exonuclease. Exo5Δ mutants are sensitive to various DNA damaging agents, particularly interstrand crosslinking agents. An epistasis analysis places exo5 + in the Fanconi pathway for interstrand crosslink repair. Exo5 + is in a redundant pathway with rad2 + , which encodes the flap endonuclease FEN1, for mitochondrial genome maintenance. Deletion of both genes lead to severe depletion of the mitochondrial genome, and defects in respiration, indicating that either spExo5 or spFEN1 is necessary for mitochondrial DNA metabolism.

Annotation

GO biological process

GO:0032042 - mitochondrial DNA metabolic process

Genes:

GO:0036298 - recombinational interstrand cross-link repair

Genes:

GO:0006302 - double-strand break repair

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GO cellular component

GO:0005739 - mitochondrion

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GO:0005634 - nucleus

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GO molecular function

GO:0051539 - 4 iron, 4 sulfur cluster binding

Genes:

GO:0045145 - single-stranded DNA 5'-3' DNA exonuclease activity

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Multi-locus phenotype

FYPO:0000490 - abnormal mitochondrial genome maintenance

Genes:

Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

Genes:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

Genes:

Genotypes:

FYPO:0003503 - normal vegetative cell length

Genes:

Genotypes:

FYPO:0000102 - sensitive to cisplatin

Genes:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

Genes:

Genotypes:

FYPO:0000268 - sensitive to UV during vegetative growth

Genes:

Genotypes:

Single locus phenotype

FYPO:0003164 - abolished nuclease activity

Genes:

Genotypes:

FYPO:0001122 - elongated vegetative cell

Genes:

Genotypes:

FYPO:0001490 - inviable elongated vegetative cell

Genes:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

Genes:

Genotypes:

FYPO:0000102 - sensitive to cisplatin

Genes:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

Genes:

Genotypes:

FYPO:0000268 - sensitive to UV during vegetative growth

Genes:

Genotypes:

FYPO:0002060 - viable vegetative cell population

Genes:

Genotypes: