Novel DNA mismatch-repair activity involving YB-1 in human mitochondria (DNA Repair, 2009, 8:704-719)

報告日期: 2009/12/15
報告時間: 16:00/16:50
報告學生: 吳長霖
講評老師: 洪建中

Novel DNA mismatch-repair activity involving YB-1 in human mitochondria


Nadja C. de Souza-Pinto, Penelope A. Mason, Kazunari Hashiguchi, Lior Weissman, Jingyan Tian, David Guay, Michel Lebel , Tinna V. Stevnsner, Lene Juel Rasmussen, Vilhelm A. Bohr

DNA Repair 8 (2009) 704–719


Speaker: Wu, Chang-Lin               

Commentator: Hung, Jan-Jong, Ph.D.    

Date: 2009/12/15

Place: Room 602, College of medicine




Damage and mutations of human mitochondrial genome (mtDNA) lead to cancer, neural diseases and aging. It is known that mtDNA is repaired by the base excision repair (BER) pathway, which removes oxidative and alkylating DNA damage. However, it is unclear how mismatches and insertion/deletion loops (IDLs) in mtDNA microsatellites are repaired. Microsatellites are simple repeated sequences and susceptible to errors during DNA replication. If replicative errors in nuclear DNA were not repaired by DNA mismatch repair (MMR) system, microsatellite instability (MSI) occurs. Both nuclear and mitochondria MSI have been detected in a variety of human cancers. Since MMR proteins have not been detected in mammalian mitochondria, in this study, authors used mitochondrial extract and DNA mismatch substrate to identify proteins that are involved in repairing mismatches and IDLs. Via the electrophoretic mobility shift assay (EMSA), authors found that mitochondrial extract had robust MMR activity. However, the mismatch-binding activity remained detectable in the mitochondrial extract prepared from MMR-deficient cell lines lacking MSH2, MSH3 or MSH6. This suggests that other mismatch-repair factors are present in mitochondria. Via affinity purification and mass spectroscopy, authors identified YB-1 as a novel factor with mismatch-binding ability in mitochondrial extract. And they also found that YB-1 could recognize the base-mismatch and +1IDL. Furthermore, they found that mutations in mtDNA increased when YB-1 were depleted from cells. In conclusion, YB-1 participates in mtDNA mismatch repair pathway via its ability in mismatch-binding and -recognition.



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