TY - JOUR
T1 - New insights and challenges in mismatch repair
T2 - Getting over the chromatin hurdle
AU - Li, Guo Min
N1 - Funding Information:
The author wishes to thank Leroy Worth for helpful comments, and acknowledge research support from the National Institutes of Health ( CA167181 and GM089684 ) and the Kentucky Lung Cancer Research Program. The author regrets omission of citations to important studies by his colleagues, that would have been included if the publisher had authorized more space for this purpose. The author holds the James-Gardner Endowed Chair in Cancer Research.
PY - 2014/7
Y1 - 2014/7
N2 - DNA mismatch repair (MMR) maintains genome stability primarily by repairing DNA replication-associated mispairs. Because loss of MMR function increases the mutation frequency genome-wide, defects in this pathway predispose affected individuals to cancer. The genes encoding essential eukaryotic MMR activities have been identified, as the recombinant proteins repair 'naked' heteroduplex DNA in vitro. However, the reconstituted system is inactive on nucleosome-containing heteroduplex DNA, and it is not understood how MMR occurs in vivo. Recent studies suggest that chromatin organization, nucleosome assembly/disassembly factors and histone modifications regulate MMR in eukaryotic cells, but the complexity and importance of the interaction between MMR and chromatin remodeling has only recently begun to be appreciated. This article reviews recent progress in understanding the mechanism of eukaryotic MMR in the context of chromatin structure and dynamics, considers the implications of these recent findings and discusses unresolved questions and challenges in understanding eukaryotic MMR.
AB - DNA mismatch repair (MMR) maintains genome stability primarily by repairing DNA replication-associated mispairs. Because loss of MMR function increases the mutation frequency genome-wide, defects in this pathway predispose affected individuals to cancer. The genes encoding essential eukaryotic MMR activities have been identified, as the recombinant proteins repair 'naked' heteroduplex DNA in vitro. However, the reconstituted system is inactive on nucleosome-containing heteroduplex DNA, and it is not understood how MMR occurs in vivo. Recent studies suggest that chromatin organization, nucleosome assembly/disassembly factors and histone modifications regulate MMR in eukaryotic cells, but the complexity and importance of the interaction between MMR and chromatin remodeling has only recently begun to be appreciated. This article reviews recent progress in understanding the mechanism of eukaryotic MMR in the context of chromatin structure and dynamics, considers the implications of these recent findings and discusses unresolved questions and challenges in understanding eukaryotic MMR.
KW - Chromatin
KW - Genetic instability
KW - H3K36me3
KW - Histone modification
KW - Mismatch repair
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U2 - 10.1016/j.dnarep.2014.03.027
DO - 10.1016/j.dnarep.2014.03.027
M3 - Article
C2 - 24767944
AN - SCOPUS:84902087071
SN - 1568-7864
VL - 19
SP - 48
EP - 54
JO - DNA Repair
JF - DNA Repair
ER -