Human Mismatch Repair Protein MSH6 Contains a PWWP Domain That Targets Double Stranded DNA. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biochemistry Année : 2008

Human Mismatch Repair Protein MSH6 Contains a PWWP Domain That Targets Double Stranded DNA.

Résumé

The eukaryotic mismatch repair (MMR) protein MSH6 exhibits a core region structurally and functionally similar to bacterial MutS. However, it possesses an additional N-terminal region (NTR), comprising a PCNA binding motif, a large region of unknown function and a nonspecific DNA binding fragment. Yeast NTR was recently described as an extended tether between PCNA and the core of MSH6 . In contrast, we show that human NTR presents a globular PWWP domain in the region of unknown function. We demonstrate that this PWWP domain binds double-stranded DNA, without any preference for mismatches or nicks, whereas its apparent affinity for single-stranded DNA is about 20 times lower. The S144I mutation, which in human MSH6 causes inherited somatic defects in MMR resulting in increased development of hereditary non polyposis colorectal cancer , is located in the DNA binding surface of the PWWP domain. However, it only moderately affects domain stability, and it does not perturb DNA binding in vitro.

Dates et versions

hal-00284767 , version 1 (03-06-2008)

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Citer

Cédric Laguri, Isabelle Duband-Goulet, Nikolas Friedrich, Marianne Axt, Pascal Belin, et al.. Human Mismatch Repair Protein MSH6 Contains a PWWP Domain That Targets Double Stranded DNA.. Biochemistry, 2008, epub ahead of print. ⟨10.1021/bi7024639⟩. ⟨hal-00284767⟩
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