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Different roles of eukaryotic MutS and MutL complexes in repair of small insertion and deletion loops in yeast.

Romanova NV, Crouse GF - PLoS Genet. (2013)

Bottom Line: Upon recognition of a mispair, the MutS complexes then interact with homologues of the bacterial MutL protein.Loops formed on the primer strand during replication lead to insertion mutations, whereas loops on the template strand lead to deletions.MutSβ is present in many eukaryotic organisms, but not in prokaryotes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Emory University, Atlanta, Georgia, United States of America.

ABSTRACT
DNA mismatch repair greatly increases genome fidelity by recognizing and removing replication errors. In order to understand how this fidelity is maintained, it is important to uncover the relative specificities of the different components of mismatch repair. There are two major mispair recognition complexes in eukaryotes that are homologues of bacterial MutS proteins, MutSα and MutSβ, with MutSα recognizing base-base mismatches and small loop mispairs and MutSβ recognizing larger loop mispairs. Upon recognition of a mispair, the MutS complexes then interact with homologues of the bacterial MutL protein. Loops formed on the primer strand during replication lead to insertion mutations, whereas loops on the template strand lead to deletions. We show here in yeast, using oligonucleotide transformation, that MutSα has a strong bias toward repair of insertion loops, while MutSβ has an even stronger bias toward repair of deletion loops. Our results suggest that this bias in repair is due to the different interactions of the MutS complexes with the MutL complexes. Two mutants of MutLα, pms1-G882E and pms1-H888R, repair deletion mispairs but not insertion mispairs. Moreover, we find that a different MutL complex, MutLγ, is extremely important, but not sufficient, for deletion repair in the presence of either MutLα mutation. MutSβ is present in many eukaryotic organisms, but not in prokaryotes. We suggest that the biased repair of deletion mispairs may reflect a critical eukaryotic function of MutSβ in mismatch repair.

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The effect of mutations in PMS1 on 2-nt in/del mispairs.Oligos were transformed into strains of the indicated genotypes and analyzed as in Figure 2; the msh2 results are those given in Figure 2.
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pgen-1003920-g003: The effect of mutations in PMS1 on 2-nt in/del mispairs.Oligos were transformed into strains of the indicated genotypes and analyzed as in Figure 2; the msh2 results are those given in Figure 2.

Mentions: A screen for mutations in PMS1 found two mutants that resulted in large increases in +1 insertions but had no effect on deletions [22]. We tested those mutations in our assay system to see if they would have a similar effect on 2-nt in/del mispairs. The results are shown in Figures 3 and S2.


Different roles of eukaryotic MutS and MutL complexes in repair of small insertion and deletion loops in yeast.

Romanova NV, Crouse GF - PLoS Genet. (2013)

The effect of mutations in PMS1 on 2-nt in/del mispairs.Oligos were transformed into strains of the indicated genotypes and analyzed as in Figure 2; the msh2 results are those given in Figure 2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814323&req=5

pgen-1003920-g003: The effect of mutations in PMS1 on 2-nt in/del mispairs.Oligos were transformed into strains of the indicated genotypes and analyzed as in Figure 2; the msh2 results are those given in Figure 2.
Mentions: A screen for mutations in PMS1 found two mutants that resulted in large increases in +1 insertions but had no effect on deletions [22]. We tested those mutations in our assay system to see if they would have a similar effect on 2-nt in/del mispairs. The results are shown in Figures 3 and S2.

Bottom Line: Upon recognition of a mispair, the MutS complexes then interact with homologues of the bacterial MutL protein.Loops formed on the primer strand during replication lead to insertion mutations, whereas loops on the template strand lead to deletions.MutSβ is present in many eukaryotic organisms, but not in prokaryotes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Emory University, Atlanta, Georgia, United States of America.

ABSTRACT
DNA mismatch repair greatly increases genome fidelity by recognizing and removing replication errors. In order to understand how this fidelity is maintained, it is important to uncover the relative specificities of the different components of mismatch repair. There are two major mispair recognition complexes in eukaryotes that are homologues of bacterial MutS proteins, MutSα and MutSβ, with MutSα recognizing base-base mismatches and small loop mispairs and MutSβ recognizing larger loop mispairs. Upon recognition of a mispair, the MutS complexes then interact with homologues of the bacterial MutL protein. Loops formed on the primer strand during replication lead to insertion mutations, whereas loops on the template strand lead to deletions. We show here in yeast, using oligonucleotide transformation, that MutSα has a strong bias toward repair of insertion loops, while MutSβ has an even stronger bias toward repair of deletion loops. Our results suggest that this bias in repair is due to the different interactions of the MutS complexes with the MutL complexes. Two mutants of MutLα, pms1-G882E and pms1-H888R, repair deletion mispairs but not insertion mispairs. Moreover, we find that a different MutL complex, MutLγ, is extremely important, but not sufficient, for deletion repair in the presence of either MutLα mutation. MutSβ is present in many eukaryotic organisms, but not in prokaryotes. We suggest that the biased repair of deletion mispairs may reflect a critical eukaryotic function of MutSβ in mismatch repair.

Show MeSH
Related in: MedlinePlus