Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations.

Lee YS, Kennedy WD, Yin YW
Cell (2009), Volume 139, Page 312
PubMed entry Publisher's site

Abstract:

Human mitochondrial DNA polymerase (Pol gamma) is the sole replicase ...
Human mitochondrial DNA polymerase (Pol gamma) is the sole replicase in mitochondria. Pol gamma is vulnerable to nonselective antiretroviral drugs and is increasingly associated with mutations found in patients with mitochondriopathies. We determined crystal structures of the human heterotrimeric Pol gamma holoenzyme and, separately, a variant of its processivity factor, Pol gammaB. The holoenzyme structure reveals an unexpected assembly of the mitochondrial DNA replicase where the catalytic subunit Pol gammaA interacts with its processivity factor primarily via a domain that is absent in all other DNA polymerases. This domain provides a structural module for supporting both the intrinsic processivity of the catalytic subunit alone and the enhanced processivity of holoenzyme. The Pol gamma structure also provides a context for interpreting the phenotypes of disease-related mutations in the polymerase and establishes a foundation for understanding the molecular basis of toxicity of anti-retroviral drugs targeting HIV reverse transcriptase.

Polymerases:

Topics:

Structure and Structure/Function, Source / Purification

Status:

new topics/pols set partial results complete validated

Results:

Polymerase Reference Property Result Context
Human Pol gamma Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Polymerase Catalytic Residue Amino Acids D890,D1135
Human Pol gamma Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Cloned or native Cloned in E. coli
Human Pol gamma Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Tagged Yes
Human Pol gamma Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Tag Name His
Human Pol gamma Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations. Full length or truncated Truncated

Entry validated by:

Structures:

3IKL

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