"Bound nucleotide controls the endonuclease activity of mismatch repair
Fukui K, Nishida M, Nakagawa N, Masui R, Kuramitsu S
DNA mismatch repair corrects mismatched base pairs mainly caused by
replication error. Recent studies revealed that human MutL endonuclease,
hPMS2, plays an essential role in the repair. However, there has been
little biochemical analysis of the MutL endonuclease. In particular, it is
unknown for what the MutL utilizes ATP binding and hydrolyzing activity.
Here we report the detailed functional analysis of Thermus thermophilus
MutL (ttMutL). ttMutL exhibited an endonuclease activity that decreased on
alteration of Asp-364 in ttMutL to Asn. The biochemical characteristics of
ttMutL were significantly affected on ATP binding, which suppressed
nonspecific DNA digestion and promoted the mismatch- and MutS-dependent
DNA binding. The inactivation of the cysteinyl residues in the C-terminal
domain resulted in the perturbation in ATP-dependent regulation of the
endonuclease activity, although the ATP-binding motif is located in the
N-terminal domain. Complementation experiments revealed that the
endonuclease activity of ttMutL and its regulation by ATP binding are
necessary for DNA repair in vivo.
This publication refers to following REPAIRtoire entries:
Last modification of this entry: Dec. 14, 2009
Add your own comment!
There is no comment yet.