Replication Protein A Prevents Promiscuous Annealing Between Short Sequence Homologies: Implications for Genome Integrity

Overview

Journal Bioessays

Publisher Wiley

Specialties Biology
Cell Biology
Molecular Biology

Date 2014 Nov 18

PMID 25400143

Citations 24

Authors

Sarah K Deng

Huan Chen

Lorraine S Symington

Affiliations

Soon will be listed here.

Abstract

Replication protein A (RPA) is the main eukaryotic single-stranded DNA (ssDNA) binding protein, having essential roles in all DNA metabolic reactions involving ssDNA. RPA binds ssDNA with high affinity, thereby preventing the formation of secondary structures and protecting ssDNA from the action of nucleases, and directly interacts with other DNA processing proteins. Here, we discuss recent results supporting the idea that one function of RPA is to prevent annealing between short repeats that can lead to chromosome rearrangements by microhomology-mediated end joining or the formation of hairpin structures that are substrates for structure-selective nucleases. We suggest that replication fork catastrophe caused by depletion of RPA could result from cleavage of secondary structures by nucleases, and that failure to cleave hairpin structures formed at DNA ends could lead to gene amplification. These studies highlight the important role RPA plays in maintaining genome integrity.

Citing Articles

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Single-strand DNA-binding protein suppresses illegitimate recombination in Escherichia coli, acting in synergy with RecQ helicase.

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The DNA double-strand break repair proteins γH2AX, RAD51, BRCA1, RPA70, KU80, and XRCC4 exhibit follicle-specific expression differences in the postnatal mouse ovaries from early to older ages.

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Hypomorphic mutation in the large subunit of replication protein A affects mutagenesis by human APOBEC cytidine deaminases in yeast.

Dennen M, Kockler Z, Roberts S, Burkholder A, Klimczak L, Gordenin D bioRxiv. 2024; .

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