Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair

Colleen C. Caldwell; Maria Spies

doi:10.1080/10409238.2020.1813070

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Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair

Journal article

Peer reviewed

Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair

Colleen C. Caldwell and Maria Spies

Critical reviews in biochemistry and molecular biology, Vol.55(5), pp.482-507

09/02/2020

DOI: 10.1080/10409238.2020.1813070

PMCID: PMC7821911

PMID: 32856505

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https://www.ncbi.nlm.nih.gov/pmc/articles/7821911View

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Abstract

The heterotrimeric eukaryotic Replication protein A (RPA) is a master regulator of numerous DNA metabolic processes. For a long time, it has been viewed as an inert protector of ssDNA and a platform for assembly of various genome maintenance and signaling machines. Later, the modular organization of the RPA DNA binding domains suggested a possibility for dynamic interaction with ssDNA. This modular organization has inspired several models for the RPA-ssDNA interaction that aimed to explain how RPA, the high-affinity ssDNA binding protein, is replaced by the downstream players in DNA replication, recombination, and repair that bind ssDNA with much lower affinity. Recent studies, and in particular single-molecule observations of RPA-ssDNA interactions, led to the development of a new model for the ssDNA handoff from RPA to a specific downstream factor where not only stability and structural rearrangements but also RPA conformational dynamics guide the ssDNA handoff. Here we will review the current knowledge of the RPA structure, its dynamic interaction with ssDNA, and how RPA conformational dynamics may be influenced by posttranslational modification and proteins that interact with RPA, as well as how RPA dynamics may be harnessed in cellular decision making.

Conformational protein dynamics

DNA repair

DNA replication

homologous recombination

protein-DNA interctions

replication protein A (RPA)

single-molecule

Details

Title: Subtitle: Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair
Creators: Colleen C. Caldwell - Roy J. and Lucille A. Carver College of Medicine
Maria Spies - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Critical reviews in biochemistry and molecular biology, Vol.55(5), pp.482-507
DOI: 10.1080/10409238.2020.1813070
PMID: 32856505
PMCID: PMC7821911
NLM abbreviation: Crit Rev Biochem Mol Biol
ISSN: 1040-9238
eISSN: 1549-7798
Publisher: Taylor & Francis
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: NIH/NIGMS R35GM131704, NIH/NCI R01 CA232425, DOD/CDMRP BC180227P1, 1836351 EAGER; name: National Institutes of Health Pharmacological Sciences Training, award: NIH T32 GM067795
Language: English
Date published: 09/02/2020
Academic Unit: Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984288726402771

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