8d33: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 16: | Line 16: | ||
Accurate replication of mitochondrial DNA (mtDNA) by DNA polymerase gamma (Polgamma) is essential for maintaining cellular energy supplies, metabolism, and cell cycle control. To illustrate the structural mechanism for Polgamma coordinating polymerase (pol) and exonuclease (exo) activities to ensure rapid and accurate DNA synthesis, we determined four cryo-EM structures of Polgamma captured after accurate or erroneous incorporation to a resolution of 2.4-3.0 A. The structures show that Polgamma employs a dual-checkpoint mechanism to sense nucleotide misincorporation and initiate proofreading. The transition from replication to error editing is accompanied by increased dynamics in both DNA and enzyme, in which the polymerase relaxes its processivity and the primer-template DNA unwinds, rotates, and backtracks to shuttle the mismatch-containing primer terminus 32 A to the exo site for editing. Our structural and functional studies also provide a foundation for analyses of Polgamma mutation-induced human diseases and aging. | Accurate replication of mitochondrial DNA (mtDNA) by DNA polymerase gamma (Polgamma) is essential for maintaining cellular energy supplies, metabolism, and cell cycle control. To illustrate the structural mechanism for Polgamma coordinating polymerase (pol) and exonuclease (exo) activities to ensure rapid and accurate DNA synthesis, we determined four cryo-EM structures of Polgamma captured after accurate or erroneous incorporation to a resolution of 2.4-3.0 A. The structures show that Polgamma employs a dual-checkpoint mechanism to sense nucleotide misincorporation and initiate proofreading. The transition from replication to error editing is accompanied by increased dynamics in both DNA and enzyme, in which the polymerase relaxes its processivity and the primer-template DNA unwinds, rotates, and backtracks to shuttle the mismatch-containing primer terminus 32 A to the exo site for editing. Our structural and functional studies also provide a foundation for analyses of Polgamma mutation-induced human diseases and aging. | ||
, PMID:37202477<ref>PMID:37202477</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
