Potential role of MLH1 in the induction of p53 and apoptosis by blocking transcription on damaged DNA templates.
作者： Mats Ljungman , Sunitha Yanamadala
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摘要: Defects in DNA mismatch repair (MMR) are common human cancers, confer tolerance to certain types of chemotherapeutic agents, and lead genomic instability. In addition their mismatch-correcting roles during replication, MMR proteins can bind lesions signal p53 apoptosis by an unknown mechanism. To further study the mechanism which protein MLH1 is involved induction apoptosis, we exposed colon carcinoma cell line HCT116 (MLH1-deficient) mlh1-corrected sublines alkylating agents or hydrogen peroxide (H2O2). It was found that while induced both phosphorylation Ser-15 site a MLH1-dependent manner, but not phosphorylation, dependent following treatment with H2O2. The did appear be cycle dependent, arguing against futile operating S phase as sole for damage signaling. Importantly, H2O2 caused significant inhibition mRNA synthesis MLH1-expressing MLH1-deficient cells. These findings suggest novel inhibiting RNA polymerase II-dependent transcription on damaged templates.
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