A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA

Yates, Luke A.; Aramayo, Ricardo; Pokhrel, Nilisha; Caldwell, Colleen C.; Kaplan, Joshua; Perera, Rajika L.; Spies, Maria; Antony, Edwin; Zhang, Xiaodong

doi:10.1038/s41467-018-07883-7

Cited by 127 publications

(194 citation statements)

References 57 publications

Supporting

Mentioning

184

Contrasting

Order By: Relevance

“…To avoid excessive DNA processing, the exonuclease activity of EXO1 is limited by ATM-mediated phosphorylation or its proceeding is inhibited by physical barriers, such as the presence of 53BP1 [ 74 ]. The single strand DNA (ssDNA) generated during the end resection process is immediately recognized and bound by the Replication Protein A (RPA) complex (RPA1, RPA2 and RPA3), which also removes secondary structures formed during the process [ 75 , 76 ]. Next, the DNA Repair Protein RAD52 mediates the removal of RPA and allows RAD51 recombinase loading onto the 3′-end of the long ssDNA.…”

Section: Dna Repair Pathwaysmentioning

confidence: 99%

DNA Damage: From Threat to Treatment

Carusillo

Mussolino

2020

Cells

150

View full text Add to dashboard Cite

DNA is the source of genetic information, and preserving its integrity is essential in order to sustain life. The genome is continuously threatened by different types of DNA lesions, such as abasic sites, mismatches, interstrand crosslinks, or single-stranded and double-stranded breaks. As a consequence, cells have evolved specialized DNA damage response (DDR) mechanisms to sustain genome integrity. By orchestrating multilayer signaling cascades specific for the type of lesion that occurred, the DDR ensures that genetic information is preserved overtime. In the last decades, DNA repair mechanisms have been thoroughly investigated to untangle these complex networks of pathways and processes. As a result, key factors have been identified that control and coordinate DDR circuits in time and space. In the first part of this review, we describe the critical processes encompassing DNA damage sensing and resolution. In the second part, we illustrate the consequences of partial or complete failure of the DNA repair machinery. Lastly, we will report examples in which this knowledge has been instrumental to develop novel therapies based on genome editing technologies, such as CRISPR-Cas.

show abstract

Section: Dna Repair Pathwaysmentioning

confidence: 99%

DNA Damage: From Threat to Treatment

Carusillo

Mussolino

2020

Cells

150

View full text Add to dashboard Cite

show abstract

“…Replication protein A is a heterotrimeric ssDNA binding protein involved in all ssDNA transactions in the nucleus. RPA has both low-and high-affinity binding modes and undergoes constant local dissociation and exchange via these modes [79]. It is required for replication, recombination, preventing spontaneous annealing of single-stranded DNA, and protecting ssDNA from degradation by nucleases.…”

Section: Rpamentioning

confidence: 99%

Regulation of Error-Prone DNA Double-Strand Break Repair and Its Impact on Genome Evolution

Hanscom

McVey

2020

Cells

View full text Add to dashboard Cite

Double-strand breaks are one of the most deleterious DNA lesions. Their repair via error-prone mechanisms can promote mutagenesis, loss of genetic information, and deregulation of the genome. These detrimental outcomes are significant drivers of human diseases, including many cancers. Mutagenic double-strand break repair also facilitates heritable genetic changes that drive organismal adaptation and evolution. In this review, we discuss the mechanisms of various error-prone DNA double-strand break repair processes and the cellular conditions that regulate them, with a focus on alternative end joining. We provide examples that illustrate how mutagenic double-strand break repair drives genome diversity and evolution. Finally, we discuss how error-prone break repair can be crucial to the induction and progression of diseases such as cancer.

show abstract

“…The high binding affinity of RPA to ssDNA is mostly mediated by four OB-fold domains OB-A, OB-B, OB-C, and OB-D in RPA70 and RPA32, while OB-F and WH domains are responsible for interacting with its protein binding partners ( Kim et al, 1994 ; Bochkareva et al, 2002 ; Fanning et al, 2006 ; Jiang et al, 2006 ). In addition, the OB-fold domains are connected by mobile loops that make RPA a flexible complex, permitting its six OB-fold domains to adopt multiple conformations ( Yates et al, 2018 ).…”

Section: Rpamentioning

confidence: 99%

Roles of OB-Fold Proteins in Replication Stress

Nguyen

Kim

Sang

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Accurate DNA replication is essential for maintaining genome stability. However, this stability becomes vulnerable when replication fork progression is stalled or slowed – a condition known as replication stress. Prolonged fork stalling can cause DNA damage, leading to genome instabilities. Thus, cells have developed several pathways and a complex set of proteins to overcome the challenge at stalled replication forks. Oligonucleotide/oligosaccharide binding (OB)-fold containing proteins are a group of proteins that play a crucial role in fork protection and fork restart. These proteins bind to single-stranded DNA with high affinity and prevent premature annealing and unwanted nuclease digestion. Among these OB-fold containing proteins, the best studied in eukaryotic cells are replication protein A (RPA) and breast cancer susceptibility protein 2 (BRCA2). Recently, another RPA-like protein complex CTC1-STN1-TEN1 (CST) complex has been found to counter replication perturbation. In this review, we discuss the latest findings on how these OB-fold containing proteins (RPA, BRCA2, CST) cooperate to safeguard DNA replication and maintain genome stability.

show abstract

A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA

Cited by 127 publications

References 57 publications

DNA Damage: From Threat to Treatment

DNA Damage: From Threat to Treatment

Regulation of Error-Prone DNA Double-Strand Break Repair and Its Impact on Genome Evolution

Roles of OB-Fold Proteins in Replication Stress

Contact Info

Product

Resources

About