000000513 001__ 513
000000513 005__ 20260217160305.0
000000513 0247_ $$2DOI$$a10.6083/M4K935H4
000000513 037__ $$aETD
000000513 245__ $$aGenetic analysis of diverse functions of DNA mismatch repair in mammalian cells
000000513 260__ $$bOregon Health and Science University
000000513 269__ $$a2010
000000513 336__ $$aDissertation
000000513 502__ $$bPh.D.
000000513 520__ $$aDNA mismatch repair (MMR) preserves genome integrity by correcting replication errors and triggering apoptosis in response to certain DNA lesions. Central to this pathway is the MutLα complex, composed of MLH1 and PMS2, whose ATPase activities are essential for repair. This study examines ATPase‑domain mutations in MLH1 and PMS2 in mammalian cells and shows that MLH1 ATPase defects impair mismatch repair and 6‑thioguanine cytotoxicity more strongly than equivalent PMS2 mutations, revealing functional asymmetry within MutLα. A second line of investigation shows that reduced expression of the nucleotide‑pool regulator DCTD increases resistance to 6‑thioguanine in human cells, whereas Dctd‑null mouse cells do not display this phenotype, suggesting adaptive maintenance of nucleotide balance. Together, these findings clarify distinct roles for MutLα subunits in repair and identify DCTD as a contributor to MMR‑dependent DNA damage responses.
000000513 540__ $$fCC BY
000000513 542__ $$fIn copyright - single owner
000000513 650__ $$aDNA-Binding Proteins$$017998
000000513 650__ $$aDNA Mismatch Repair$$037646
000000513 650__ $$aDCMP Deaminase$$017596
000000513 650__ $$aMice$$036842
000000513 650__ $$aMismatch Repair Endonuclease PMS2$$011653
000000513 6531_ $$amlh1 protein
000000513 691__ $$aSchool of Medicine$$041369
000000513 692__ $$aDepartment of Molecular and Medical Genetics$$041428
000000513 7001_ $$aJohnson, Jennifer$$uOregon Health and Science University$$041354
000000513 7201_ $$aLiskay, R. Michael$$uOregon Health and Science University$$041354$$7Personal$$eMentor$$eAdvisor
000000513 8564_ $$9649f58c9-5c2f-4587-9178-23c2dc1d768c$$s1398852$$uhttps://digitalcollections.ohsu.edu/record/513/files/514_etd.pdf$$ePublic$$2650edbdf4064e620c30a96d558d3b1af$$31
000000513 905__ $$a/rest/prod/n8/70/zq/87/n870zq87z
000000513 909CO $$ooai:digitalcollections.ohsu.edu:513$$pstudent-work
000000513 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000513 980__ $$aTheses and Dissertations