Endonucleolytic Function of MutLα in Human Mismatch Repair

@article{Kadyrov2006EndonucleolyticFO,
  title={Endonucleolytic Function of MutL$\alpha$ in Human Mismatch Repair},
  author={Farid A Kadyrov and Leonid Dzantiev and Nicoleta Constantin and Paul L. Modrich},
  journal={Cell},
  year={2006},
  volume={126},
  pages={297-308}
}
Summary Half of hereditary nonpolyposis colon cancer kindreds harbor mutations that inactivate MutLα (MLH1•PMS2 heterodimer). MutLα is required for mismatch repair, but its function in this process is unclear. We show that human MutLα is a latent endonuclease that is activated in a mismatch-, MutSα-, RFC-, PCNA-, and ATP-dependent manner. Incision of a nicked mismatch-containing DNA heteroduplex by this four-protein system is strongly biased to the nicked strand. A mismatch-containing DNA… 

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TLDR
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TLDR
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TLDR
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TLDR
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Interaction of proliferating cell nuclear antigen with PMS2 is required for MutLα activation and function in mismatch repair
TLDR
It is shown that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends on PCNA interaction with the C-terminal endonuclease domain of the MutL α PMS2 subunit.
The functions of MutL in mismatch repair: the power of multitasking.
  • A. Guarné
  • Chemistry, Medicine
    Progress in molecular biology and translational science
  • 2012
TLDR
This chapter discusses how the endonuclease activity of MutL is regulated by other repair factors and unveils yet another crucial function of the MutL protein at the strand discrimination step in DNA mismatch repair.
Structure of the endonuclease domain of MutL: unlicensed to cut.
TLDR
The structure unveils a powerful inhibitory mechanism to prevent undesired nicking of newly replicated DNA and allows us to propose a model describing how the interaction with MutS and the processivity clamp could license the endonuclease activity of MutL.
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