Research output: Contribution to journal › Article › peer-review
The fidelity of DNA replication, particularly on GC-rich templates, is reduced by defects of the Fe-S cluster in DNA polymerase δ. / Kiktev, Denis A.; Dominska, Margaret; Zhang, Tony; Dahl, Joseph; Stepchenkova, Elena I.; Mieczkowski, Piotr; Burgers, Peter M.; Lujan, Scott; Burkholder, Adam; Kunkel, Thomas A.; Petes, Thomas D.
In: Nucleic Acids Research, Vol. 49, No. 10, 04.06.2021, p. 5623-5636.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - The fidelity of DNA replication, particularly on GC-rich templates, is reduced by defects of the Fe-S cluster in DNA polymerase δ
AU - Kiktev, Denis A.
AU - Dominska, Margaret
AU - Zhang, Tony
AU - Dahl, Joseph
AU - Stepchenkova, Elena I.
AU - Mieczkowski, Piotr
AU - Burgers, Peter M.
AU - Lujan, Scott
AU - Burkholder, Adam
AU - Kunkel, Thomas A.
AU - Petes, Thomas D.
N1 - Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2021/6/4
Y1 - 2021/6/4
N2 - Iron-sulfur clusters (4Fe-4S) exist in many enzymes concerned with DNA replication and repair. The contribution of these clusters to enzymatic activity is not fully understood. We identified the MET18 (MMS19) gene of Saccharomyces cerevisiae as a strong mutator on GC-rich genes. Met18p is required for the efficient insertion of iron-sulfur clusters into various proteins. met18 mutants have an elevated rate of deletions between short flanking repeats, consistent with increased DNA polymerase slippage. This phenotype is very similar to that observed in mutants of POL3 (encoding the catalytic subunit of Pol δ) that weaken binding of the iron-sulfur cluster. Comparable mutants of POL2 (Pol Ïμ) do not elevate deletions. Further support for the conclusion that met18 strains result in impaired DNA synthesis by Pol δare the observations that Pol δisolated from met18 strains has less bound iron and is less processive in vitro than the wild-type holoenzyme.
AB - Iron-sulfur clusters (4Fe-4S) exist in many enzymes concerned with DNA replication and repair. The contribution of these clusters to enzymatic activity is not fully understood. We identified the MET18 (MMS19) gene of Saccharomyces cerevisiae as a strong mutator on GC-rich genes. Met18p is required for the efficient insertion of iron-sulfur clusters into various proteins. met18 mutants have an elevated rate of deletions between short flanking repeats, consistent with increased DNA polymerase slippage. This phenotype is very similar to that observed in mutants of POL3 (encoding the catalytic subunit of Pol δ) that weaken binding of the iron-sulfur cluster. Comparable mutants of POL2 (Pol Ïμ) do not elevate deletions. Further support for the conclusion that met18 strains result in impaired DNA synthesis by Pol δare the observations that Pol δisolated from met18 strains has less bound iron and is less processive in vitro than the wild-type holoenzyme.
KW - Catalytic Domain
KW - DNA Polymerase III/metabolism
KW - DNA Repair
KW - DNA Replication
KW - DNA-Directed DNA Polymerase/metabolism
KW - Iron-Sulfur Proteins/metabolism
KW - Protein Binding
KW - Saccharomyces cerevisiae Proteins/metabolism
KW - Saccharomyces cerevisiae/genetics
KW - Transcription Factors/metabolism
KW - MUTATION-RATE
KW - MICROSATELLITE
KW - MISMATCH REPAIR
KW - SACCHAROMYCES-CEREVISIAE
KW - BASE
KW - GENE
KW - GENOME-WIDE ANALYSIS
KW - DELETIONS
KW - DOMAINS
KW - SUBUNIT
UR - http://www.scopus.com/inward/record.url?scp=85108124225&partnerID=8YFLogxK
U2 - 10.1093/nar/gkab371
DO - 10.1093/nar/gkab371
M3 - Article
C2 - 34019669
AN - SCOPUS:85108124225
VL - 49
SP - 5623
EP - 5636
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 10
ER -
ID: 88539255