Editing DNA replication and recombination by mismatch repair: from bacterial genetics to mechanisms of predisposition to cancer in humans

1995 ◽  
pp. 93-99
Author(s):  
M. Radman ◽  
I. Matic ◽  
J. A. Halliday ◽  
F. Taddei
Keyword(s):  
Dna Replication ◽  
Mismatch Repair ◽  
Bacterial Genetics

scholarly journals Mutations in the Bacillus subtilis β Clamp That Separate Its Roles in DNA Replication from Mismatch Repair

2010 ◽  
Vol 192 (13) ◽  
pp. 3452-3463 ◽  
Author(s):  
Nicole M. Dupes ◽  
Brian W. Walsh ◽  
Andrew D. Klocko ◽  
Justin S. Lenhart ◽  
Heather L. Peterson ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Dna Replication ◽  
Mismatch Repair ◽  
Mutation Frequency ◽  
Elevated Temperatures ◽  
Temperature Sensitive ◽  
Mutant Form ◽  
Appreciable Effect ◽  
Missense Mutations ◽  
Dna Mismatch

ABSTRACT The β clamp is an essential replication sliding clamp required for processive DNA synthesis. The β clamp is also critical for several additional aspects of DNA metabolism, including DNA mismatch repair (MMR). The dnaN5 allele of Bacillus subtilis encodes a mutant form of β clamp containing the G73R substitution. Cells with the dnaN5 allele are temperature sensitive for growth due to a defect in DNA replication at 49°C, and they show an increase in mutation frequency caused by a partial defect in MMR at permissive temperatures. We selected for intragenic suppressors of dnaN5 that rescued viability at 49°C to determine if the DNA replication defect could be separated from the MMR defect. We isolated three intragenic suppressors of dnaN5 that restored growth at the nonpermissive temperature while maintaining an increase in mutation frequency. All three dnaN alleles encoded the G73R substitution along with one of three novel missense mutations. The missense mutations isolated were S22P, S181G, and E346K. Of these, S181G and E346K are located near the hydrophobic cleft of the β clamp, a common site occupied by proteins that bind the β clamp. Using several methods, we show that the increase in mutation frequency resulting from each dnaN allele is linked to a defect in MMR. Moreover, we found that S181G and E346K allowed growth at elevated temperatures and did not have an appreciable effect on mutation frequency when separated from G73R. Thus, we found that specific residue changes in the B. subtilis β clamp separate the role of the β clamp in DNA replication from its role in MMR.

Mismatch repair of heteroduplex DNA intermediates of extrachromosomal recombination in mammalian cells

1994 ◽  
Vol 14 (1) ◽  
pp. 400-406
Author(s):  
W P Deng ◽  
J A Nickoloff
Keyword(s):  
Dna Replication ◽  
Mismatch Repair ◽  
Mammalian Cells ◽  
Strand Break ◽  
Wild Type ◽  
Heteroduplex Dna ◽  
Frameshift Mutations ◽  
Single Strand Annealing ◽  
Extrachromosomal Recombination ◽  
Strand Annealing

Previous work indicated that extrachromosomal recombination in mammalian cells could be explained by the single-strand annealing (SSA) model. This model predicts that extrachromosomal recombination leads to nonconservative crossover products and that heteroduplex DNA (hDNA) is formed by annealing of complementary single strands. Mismatched bases in hDNA may subsequently be repaired to wild-type or mutant sequences, or they may remain unrepaired and segregate following DNA replication. We describe a system to examine the formation and mismatch repair of hDNA in recombination intermediates. Our results are consistent with extrachromosomal recombination occurring via SSA and producing crossover recombinant products. As predicted by the SSA model, hDNA was present in double-strand break-induced recombination intermediates. By placing either silent or frameshift mutations in the predicted hDNA region, we have shown that mismatches are efficiently repaired prior to DNA replication.

scholarly journals Phosphorylation of PCNA by EGFR inhibits mismatch repair and promotes misincorporation during DNA synthesis

2015 ◽  
Vol 112 (18) ◽  
pp. 5667-5672 ◽  
Author(s):  
Janice Ortega ◽  
Jessie Y. Li ◽  
Sanghee Lee ◽  
Dan Tong ◽  
Liya Gu ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Mismatch Repair ◽  
Posttranslational Modifications ◽  
Growth Factor Receptor ◽  
Nuclear Antigen ◽  
Dna Mismatch ◽  
Epidermal Growth ◽  
Mismatch Recognition ◽  
Proliferating Cell

Proliferating cell nuclear antigen (PCNA) plays essential roles in eukaryotic cells during DNA replication, DNA mismatch repair (MMR), and other events at the replication fork. Earlier studies show that PCNA is regulated by posttranslational modifications, including phosphorylation of tyrosine 211 (Y211) by the epidermal growth factor receptor (EGFR). However, the functional significance of Y211-phosphorylated PCNA remains unknown. Here, we show that PCNA phosphorylation by EGFR alters its interaction with mismatch-recognition proteins MutSα and MutSβ and interferes with PCNA-dependent activation of MutLα endonuclease, thereby inhibiting MMR at the initiation step. Evidence is also provided that Y211-phosphorylated PCNA induces nucleotide misincorporation during DNA synthesis. These findings reveal a novel mechanism by which Y211-phosphorylated PCNA promotes cancer development and progression via facilitating error-prone DNA replication and suppressing the MMR function.

scholarly journals Mismatch Repair, But Not Heteroduplex Rejection, Is Temporally Coupled to DNA Replication

Science ◽  
2011 ◽  
Vol 334 (6063) ◽  
pp. 1713-1716 ◽  
Author(s):  
H. Hombauer ◽  
A. Srivatsan ◽  
C. D. Putnam ◽  
R. D. Kolodner
Keyword(s):  
Dna Replication ◽  
Mismatch Repair ◽  
Heteroduplex Rejection

scholarly journals DNA Replication and Postreplication Mismatch Repair in Cell-Free Extracts from Cultured Human Neuroblastoma and Fibroblast Cells

1997 ◽  
Vol 17 (22) ◽  
pp. 8711-8720 ◽  
Author(s):  
Pascale David ◽  
Edna Efrati ◽  
Georges Tocco ◽  
Sharon Wald Krauss ◽  
Myron F. Goodman
Keyword(s):  
Dna Replication ◽  
Mismatch Repair ◽  
Fibroblast Cells ◽  
Human Neuroblastoma

Involvement of Escherichia coli Mismatch Repair in DNA Replication and Recombination

1984 ◽  
Vol 49 (0) ◽  
pp. 611-615 ◽  
Author(s):  
R. Wagner ◽  
C. Dohet ◽  
M. Jones ◽  
M.-P. Doutriaux ◽  
F. Hutchinson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Mismatch Repair
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