TY - JOUR
T1 - Evidence that nucleosomes inhibit mismatch repair in eukaryotic cells
AU - Li, Feng
AU - Tian, Lei
AU - Gu, Liya
AU - Li, Guo Min
PY - 2009/11/27
Y1 - 2009/11/27
N2 - The influence of chromatin structure on DNA metabolic processes, including DNA replication and repair, has been a matter of intensive studies in recent years. Although the human mismatch repair (MMR) reaction has been reconstituted using purified proteins, the influence of chromatin structure on human MMR is unknown. This study examines the interaction between human MutSα and a mismatch located within a nucleosome or between two nucleosomes. The results show that, whereas MutSα specifically recognizes both types of nucleosomal heteroduplexes, the protein bound the mismatch within a nucleosome with much lower efficiency than a naked heteroduplex or a heterology free of histone proteins but between two nucleosomes. Additionally, MutSα displays reduced ATPase- and ADP-binding activity when interacting with nucleosomal heteroduplexes. Interestingly, nucleosomes block ATP-induced MutSα sliding along the DNA helix when the mismatch is in between two nucleosomes. These findings suggest that nucleosomes may inhibit MMR in eukaryotic cells. The implications of these findings for our understanding of eukaryotic MMR are discussed.
AB - The influence of chromatin structure on DNA metabolic processes, including DNA replication and repair, has been a matter of intensive studies in recent years. Although the human mismatch repair (MMR) reaction has been reconstituted using purified proteins, the influence of chromatin structure on human MMR is unknown. This study examines the interaction between human MutSα and a mismatch located within a nucleosome or between two nucleosomes. The results show that, whereas MutSα specifically recognizes both types of nucleosomal heteroduplexes, the protein bound the mismatch within a nucleosome with much lower efficiency than a naked heteroduplex or a heterology free of histone proteins but between two nucleosomes. Additionally, MutSα displays reduced ATPase- and ADP-binding activity when interacting with nucleosomal heteroduplexes. Interestingly, nucleosomes block ATP-induced MutSα sliding along the DNA helix when the mismatch is in between two nucleosomes. These findings suggest that nucleosomes may inhibit MMR in eukaryotic cells. The implications of these findings for our understanding of eukaryotic MMR are discussed.
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U2 - 10.1074/jbc.M109.049874
DO - 10.1074/jbc.M109.049874
M3 - Article
C2 - 19808662
AN - SCOPUS:70450237030
SN - 0021-9258
VL - 284
SP - 33056
EP - 33061
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 48
ER -