Cadmium inhibits human DNA mismatch repair in vivo

2004 ◽  
Vol 321 (1) ◽  
pp. 21-25 ◽  
Author(s):  
Anne Lützen ◽  
Sascha Emilie Liberti ◽  
Lene Juel Rasmussen
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Dna Mismatch ◽  
Human Dna

scholarly journals Steady-state regulation of the human DNA mismatch repair system.

2000 ◽  
Vol 275 (37) ◽  
pp. 29178
Author(s):  
Dong Kyung Chang ◽  
Luigi Ricciardiello ◽  
Ajay Goel ◽  
Christina L. Chang ◽  
C. Richard Boland
Keyword(s):  
Steady State ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
State Regulation ◽  
Repair System ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

scholarly journals Nuclear localization of human DNA mismatch repair protein exonuclease 1 (hEXO1)

2007 ◽  
Vol 35 (8) ◽  
pp. 2609-2619 ◽  
Author(s):  
Nina Østergaard Knudsen ◽  
Finn Cilius Nielsen ◽  
Lena Vinther ◽  
Ronni Bertelsen ◽  
Steen Holten-Andersen ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Nuclear Localization ◽  
Dna Mismatch Repair ◽  
Dna Mismatch ◽  
Human Dna ◽  
Repair Protein ◽  
Exonuclease 1 ◽  
Mismatch Repair Protein

scholarly journals The Bloom's Syndrome Helicase Interacts Directly with the Human DNA Mismatch Repair Protein hMSH6

2003 ◽  
Vol 384 (8) ◽  
Author(s):  
G. Pedrazzi ◽  
C. Z. Bachrati ◽  
N. Selak ◽  
I. Studer ◽  
M. Petkovic ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Bloom's Syndrome ◽  
Dna Mismatch ◽  
Human Dna ◽  
Repair Protein ◽  
Bloom’S Syndrome ◽  
Mismatch Repair Protein

Oxidative stress inactivates the human DNA mismatch repair system

2002 ◽  
Vol 283 (1) ◽  
pp. C148-C154 ◽  
Author(s):  
Christina L. Chang ◽  
Giancarlo Marra ◽  
Dharam P. Chauhan ◽  
Hannah T. Ha ◽  
Dong K. Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mismatch Repair ◽  
Chronic Inflammation ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Microsatellites ◽  
Single Base ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System

In the human DNA mismatch repair (MMR) system, hMSH2 forms the hMutSα and hMutSβ complexes with hMSH6 and hMSH3, respectively, whereas hMLH1 and hPMS2 form the hMutLα heterodimer. These complexes, together with other components in the MMR system, correct single-base mismatches and small insertion/deletion loops that occur during DNA replication. Microsatellite instability (MSI) occurs when the loops in DNA microsatellites are not corrected because of a malfunctioning MMR system. Low-frequency MSI (MSI-L) is seen in some chronically inflamed tissues in the absence of genetic inactivation of the MMR system. We hypothesize that oxidative stress associated with chronic inflammation might damage protein components of the MMR system, leading to its functional inactivation. In this study, we demonstrate that noncytotoxic levels of H2O2 inactivate both single-base mismatch and loop repair activities of the MMR system in a dose-dependent fashion. On the basis of in vitro complementation assays using recombinant MMR proteins, we show that this inactivation is most likely due to oxidative damage to hMutSα, hMutSβ, and hMutLα protein complexes. We speculate that inactivation of the MMR function in response to oxidative stress may be responsible for the MSI-L seen in nonneoplastic and cancer tissues associated with chronic inflammation.

scholarly journals Structural characterization of transient interactions in DNA mismatch repair

2014 ◽  
Vol 70 (a1) ◽  
pp. C418-C418
Author(s):  
Monica Pillon ◽  
Vignesh Babu ◽  
Mark Sutton ◽  
Alba Guarne
Keyword(s):  
Complex Formation ◽  
Mismatch Repair ◽  
Structural Characterization ◽  
Dna Mismatch Repair ◽  
Full Length ◽  
Endonuclease Activity ◽  
Dimerization Domain ◽  
Dna Mismatch ◽  
Replication Errors

DNA mismatch repair (MMR) is a conserved pathway that safeguards genome integrity by correcting replication errors. The initiation of MMR is orchestrated by two proteins –MutS and MutL. MutS detects replication errors and recruits MutL, a key regulator in coordinating downstream MMR events. The processivity clamp, typically known to tether the replicative polymerase to DNA during DNA synthesis, also has a role in several steps in MMR. We have previously shown that MutL transiently interacts with the clamp and that this complex is important for MMR in vivo. The role of the clamp in eukaryotes and most bacteria is believed to license MutL endonuclease activity. In bacterial organisms where MutL does not have endonuclease activity, such as in Escherichia coli, the clamp also interacts with MutL and this interaction is also important for MMR activity. However, the transient nature of this complex prevents its functional and structural characterization. Here, we develop a method to stabilize the E. coli MutL-clamp complex by engineering a disulfide bond at the known protein complex interface and characterize its structure using small angle X-ray scattering (SAXS). MutL binds the clamp through a consensus motif found in its dimerization domain. Using this domain (MutL-CTD) we monitor complex formation with the clamp. We observe two complexes using SAXS. In one complex the MutL-CTD occupies a single hydrophobic cleft of the clamp, while the other occupies both hydrophobic clefts simultaneously. To identify the physiological complex, we used the full length MutL protein to impose further constraints. Analysis of complex formation suggests that full length MutL binds a single cleft on the clamp. Altogether, our data reveals how MutL interacts with the clamp in the early steps of MMR and this approach could be implemented to structurally characterize other transient complexes, an aspect of structural biology that is largely unexplored.

scholarly journals Functional Studies on the Candidate ATPase Domains of Saccharomyces cerevisiae MutLα

2000 ◽  
Vol 20 (17) ◽  
pp. 6390-6398 ◽  
Author(s):  
Phuoc T. Tran ◽  
R. Michael Liskay
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mismatch Repair ◽  
Conformational Changes ◽  
Atp Hydrolysis ◽  
Dna Mismatch Repair ◽  
Limited Proteolysis ◽  
Atp Binding ◽  
Dna Mismatch ◽  
Functional Studies

ABSTRACT Saccharomyces cerevisiae MutL homologues Mlh1p and Pms1p form a heterodimer, termed MutLα, that is required for DNA mismatch repair after mismatch binding by MutS homologues. Recent sequence and structural studies have placed the NH2 termini of MutL homologues in a new family of ATPases. To address the functional significance of this putative ATPase activity in MutLα, we mutated conserved motifs for ATP hydrolysis and ATP binding in both Mlh1p and Pms1p and found that these changes disrupted DNA mismatch repair in vivo. Limited proteolysis with purified recombinant MutLα demonstrated that the NH2 terminus of MutLα undergoes conformational changes in the presence of ATP and nonhydrolyzable ATP analogs. Furthermore, two-hybrid analysis suggested that these ATP-binding-induced conformational changes promote an interaction between the NH2 termini of Mlh1p and Pms1p. Surprisingly, analysis of specific mutants suggested differential requirements for the ATPase motifs of Mlh1p and Pms1p during DNA mismatch repair. Taken together, these results suggest that MutLα undergoes ATP-dependent conformational changes that may serve to coordinate downstream events during yeast DNA mismatch repair.

In vivo DNA mismatch repair measurement in zebrafish embryos and its use in screening of environmental carcinogens

2016 ◽  
Vol 302 ◽  
pp. 296-303 ◽  
Author(s):  
Yuanhong Chen ◽  
Changjiang Huang ◽  
Chenglian Bai ◽  
Changchun Du ◽  
Junhua Liao ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Zebrafish Embryos ◽  
Environmental Carcinogens ◽  
Dna Mismatch

scholarly journals Evidence for Involvement of HMGB1 Protein in Human DNA Mismatch Repair

2004 ◽  
Vol 279 (20) ◽  
pp. 20935-20940 ◽  
Author(s):  
Fenghua Yuan ◽  
Liya Gu ◽  
Shuangli Guo ◽  
Chunmei Wang ◽  
Guo-Min Li
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Hmgb1 Protein ◽  
Dna Mismatch ◽  
Human Dna
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