2o8d: Difference between revisions
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==Overview== | ==Overview== | ||
Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates | Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates the cellular response to certain classes of DNA damage, and has been implicated in the generation of immune diversity. Each of these functions depends on MutSalpha (MSH2*MSH6 heterodimer). Inactivation of this protein complex is responsible for tumor development in about half of known hereditary nonpolyposis colorectal cancer kindreds and also occurs in sporadic tumors in a variety of tissues. Here, we describe a series of crystal structures of human MutSalpha bound to different DNA substrates, each known to elicit one of the diverse biological responses of the MMR pathway. All lesions are recognized in a similar manner, indicating that diversity of MutSalpha-dependent responses to DNA lesions is generated in events downstream of this lesion recognition step. This study also allows rigorous mapping of cancer-causing mutations and furthermore suggests structural pathways for allosteric communication between different regions within the heterodimer. | ||
==Disease== | |||
Known diseases associated with this structure: Colorectal cancer, hereditary nonpolyposis, type 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Colorectal cancer, hereditary nonpolyposis, type 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600678 600678]], Endometrial cancer, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600678 600678]], Mismatch repair cancer syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600678 600678]], Mismatch repair cancer syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Muir-Torre syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Ovarian cancer, endometrial type. 608089 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600678 600678]] | |||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
Structure of the | Structure of the human MutSalpha DNA lesion recognition complex., Warren JJ, Pohlhaus TJ, Changela A, Iyer RR, Modrich PL, Beese LS, Mol Cell. 2007 May 25;26(4):579-92. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17531815 17531815] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Beese, L | [[Category: Beese, L S.]] | ||
[[Category: Changela, A.]] | [[Category: Changela, A.]] | ||
[[Category: Modrich, P | [[Category: Modrich, P L.]] | ||
[[Category: Pohlhaus, T | [[Category: Pohlhaus, T J.]] | ||
[[Category: Warren, J | [[Category: Warren, J J.]] | ||
[[Category: ADP]] | [[Category: ADP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: somatic hypermutation]] | [[Category: somatic hypermutation]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:15:36 2008'' | ||
Revision as of 19:15, 21 February 2008
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human MutSalpha (MSH2/MSH6) bound to ADP and a G dU mispair
OverviewOverview
Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates the cellular response to certain classes of DNA damage, and has been implicated in the generation of immune diversity. Each of these functions depends on MutSalpha (MSH2*MSH6 heterodimer). Inactivation of this protein complex is responsible for tumor development in about half of known hereditary nonpolyposis colorectal cancer kindreds and also occurs in sporadic tumors in a variety of tissues. Here, we describe a series of crystal structures of human MutSalpha bound to different DNA substrates, each known to elicit one of the diverse biological responses of the MMR pathway. All lesions are recognized in a similar manner, indicating that diversity of MutSalpha-dependent responses to DNA lesions is generated in events downstream of this lesion recognition step. This study also allows rigorous mapping of cancer-causing mutations and furthermore suggests structural pathways for allosteric communication between different regions within the heterodimer.
DiseaseDisease
Known diseases associated with this structure: Colorectal cancer, hereditary nonpolyposis, type 1 OMIM:[609309], Colorectal cancer, hereditary nonpolyposis, type 5 OMIM:[600678], Endometrial cancer, familial OMIM:[600678], Mismatch repair cancer syndrome OMIM:[600678], Mismatch repair cancer syndrome OMIM:[609309], Muir-Torre syndrome OMIM:[609309], Ovarian cancer, endometrial type. 608089 OMIM:[600678]
About this StructureAbout this Structure
2O8D is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the human MutSalpha DNA lesion recognition complex., Warren JJ, Pohlhaus TJ, Changela A, Iyer RR, Modrich PL, Beese LS, Mol Cell. 2007 May 25;26(4):579-92. PMID:17531815
Page seeded by OCA on Thu Feb 21 18:15:36 2008