scholarly journals Cascading MutS and MutL sliding clamps control DNA diffusion to activate mismatch repair

Nature ◽  
2016 ◽  
Vol 539 (7630) ◽  
pp. 583-587 ◽  
Author(s):  
Jiaquan Liu ◽  
Jeungphill Hanne ◽  
Brooke M. Britton ◽  
Jared Bennett ◽  
Daehyung Kim ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Dna Diffusion ◽  
Sliding Clamps

scholarly journals MutL sliding clamps coordinate exonuclease-independent Escherichia coli mismatch repair

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiaquan Liu ◽  
Ryanggeun Lee ◽  
Brooke M. Britton ◽  
James A. London ◽  
Keunsang Yang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Single Molecule ◽  
Single Stranded Dna ◽  
Mismatched Dna ◽  
Sliding Clamps ◽  
Unwinding Dynamics ◽  
Exonuclease Digestion

AbstractA shared paradigm of mismatch repair (MMR) across biology depicts extensive exonuclease-driven strand-specific excision that begins at a distant single-stranded DNA (ssDNA) break and proceeds back past the mismatched nucleotides. Historical reconstitution studies concluded that Escherichia coli (Ec) MMR employed EcMutS, EcMutL, EcMutH, EcUvrD, EcSSB and one of four ssDNA exonucleases to accomplish excision. Recent single-molecule images demonstrated that EcMutS and EcMutL formed cascading sliding clamps on a mismatched DNA that together assisted EcMutH in introducing ssDNA breaks at distant newly replicated GATC sites. Here we visualize the complete strand-specific excision process and find that long-lived EcMutL sliding clamps capture EcUvrD helicase near the ssDNA break, significantly increasing its unwinding processivity. EcSSB modulates the EcMutL–EcUvrD unwinding dynamics, which is rarely accompanied by extensive ssDNA exonuclease digestion. Together these observations are consistent with an exonuclease-independent MMR strand excision mechanism that relies on EcMutL–EcUvrD helicase-driven displacement of ssDNA segments between adjacent EcMutH–GATC incisions.

scholarly journals Dynamic control of strand excision during human DNA mismatch repair

2016 ◽  
Vol 113 (12) ◽  
pp. 3281-3286 ◽  
Author(s):  
Yongmoon Jeon ◽  
Daehyung Kim ◽  
Juana V. Martín-López ◽  
Ryanggeun Lee ◽  
Jungsic Oh ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Single Molecule ◽  
Dynamic Control ◽  
Tract Length ◽  
Dna Mismatch ◽  
Cell Extracts ◽  
Evolutionarily Conserved ◽  
Sliding Clamps ◽  
Dna Scission ◽  
Gapped Dna

Mismatch repair (MMR) is activated by evolutionarily conserved MutS homologs (MSH) and MutL homologs (MLH/PMS). MSH recognizes mismatched nucleotides and form extremely stable sliding clamps that may be bound by MLH/PMS to ultimately authorize strand-specific excision starting at a distant 3′- or 5′-DNA scission. The mechanical processes associated with a complete MMR reaction remain enigmatic. The purified human (Homo sapien or Hs) 5′-MMR excision reaction requires the HsMSH2–HsMSH6 heterodimer, the 5′ → 3′ exonuclease HsEXOI, and the single-stranded binding heterotrimer HsRPA. The HsMLH1–HsPMS2 heterodimer substantially influences 5′-MMR excision in cell extracts but is not required in the purified system. Using real-time single-molecule imaging, we show that HsRPA or Escherichia coli EcSSB restricts HsEXOI excision activity on nicked or gapped DNA. HsMSH2–HsMSH6 activates HsEXOI by overcoming HsRPA/EcSSB inhibition and exploits multiple dynamic sliding clamps to increase tract length. Conversely, HsMLH1–HsPMS2 regulates tract length by controlling the number of excision complexes, providing a link to 5′ MMR.

scholarly journals Mismatch repair protein hMSH2-hMSH6 recognizes mismatches and forms sliding clamps within a D-loop recombination intermediate

2014 ◽  
Vol 111 (3) ◽  
pp. E316-E325 ◽  
Author(s):  
M. Honda ◽  
Y. Okuno ◽  
S. R. Hengel ◽  
J. V. Martin-Lopez ◽  
C. P. Cook ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Repair Protein ◽  
Sliding Clamps ◽  
D Loop ◽  
Mismatch Repair Protein

Low Frequency of Mismatch Repair Deficiency in a Large Cohort of Non-liver fluke associated Cholangiocarcinomas

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
B Goeppert ◽  
S Roessler ◽  
M Renner ◽  
S Singer ◽  
A Mehrabi ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Liver Fluke ◽  
Low Frequency ◽  
Large Cohort ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency

Mismatch-Repair-Defekt-Analyse bei 191 konsekutiven Endometriumkarzinom-Patientinnen

2018 ◽  
Author(s):  
N Pauly ◽  
A du Bois ◽  
P Harter ◽  
T Baert ◽  
F Heitz ◽  
...  
Keyword(s):  
Mismatch Repair
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