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DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation

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The human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader.

Feng Wang¹, Qing He¹, Nina Y Yao²

¹Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.

Nature Structural & Molecular Biology

|June 13, 2024

Summary

This summary is machine-generated.

The ATAD5-RFC complex exclusively unloads proliferating cell nuclear antigen (PCNA) from DNA due to unique structural features. These features, including locking loops and a DNA-binding chamber plug, prevent DNA binding and explain its unloading function.

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Area of Science:

Molecular Biology
Structural Biology
Biochemistry

Background:

Proliferating cell nuclear antigen (PCNA) is loaded onto DNA by clamp-loading complexes like RFC and CTF18-RFC.
ATAD5-RFC is a distinct complex that exclusively unloads PCNA from DNA, but its structural mechanism remains unclear.

Purpose of the Study:

To elucidate the structural basis of ATAD5-RFC's exclusive PCNA unloading function.
To understand how ATAD5-RFC differs structurally from PCNA loaders.

Main Methods:

Structural analysis of the ATAD5-RFC complex.
Observation of intermediate states of PCNA bound to ATAD5-RFC.

Main Results:

ATAD5 possesses unique locking loops and a domain that obstructs the DNA-binding chamber, creating a rigid structure.
These structural elements prevent the conformational changes necessary for DNA binding, thus explaining ATAD5-RFC's unloading role.
ATAD5-RFC unloads PCNA by opening a unique gap between PCNA protomers 2 and 3, distinct from previously observed loader mechanisms.
Similar structural features are conserved in the yeast homolog, Elg1-RFC.

Conclusions:

The unique structure of ATAD5-RFC dictates its function as a PCNA unloader.
ATAD5-RFC utilizes a novel mechanism for PCNA unloading, involving a distinct protomer gap.
Structural insights into ATAD5-RFC provide a deeper understanding of DNA clamp dynamics and regulation.