Human Primpol1: a novel guardian of stalled replication forks

Im, Jun‐Sub; Lee, Kyung Yong; Dillon, Laura W.; Dutta, Anindya

doi:10.1038/embor.2013.171

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…Besides SLFN11, RPA interacts with a large number of proteins involved in DNA replication, cell cycle regulation, and DNA repair and has been considered as a platform that promotes critical biochemical reactions that occur at ssDNA. For example, we and several other groups have demonstrated that hPrimpol1/CCDC111/Primpol , the PSO4/PRP19 complex , HARP/SMARCAL1 , and several other proteins possessing enzymatic activities can be recruited to sites of DNA damage through the direct interaction with RPA. While SLFN11 inhibits checkpoint maintenance and HR repair, almost all the known RPA‐binding proteins positively regulate DNA damage response.…”

Section: Discussionmentioning

confidence: 96%

SLFN 11 inhibits checkpoint maintenance and homologous recombination repair

et al. 2015

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High expression levels of SLFN11 correlate with the sensitivity of human cancer cells to DNA-damaging agents. However, little is known about the underlying mechanism. Here, we show that SLFN11 interacts directly with RPA1 and is recruited to sites of DNA damage in an RPA1-dependent manner. Furthermore, we establish that SLFN11 inhibits checkpoint maintenance and homologous recombination repair by promoting the destabilization of the RPA-ssDNA complex, thereby sensitizing cancer cell lines expressing high endogenous levels of SLFN11 to DNA-damaging agents. Finally, we demonstrate that the RPA1-binding ability of SLFN11 is required for its function in the DNA damage response. Our findings not only provide novel insight into the molecular mechanisms underlying the drug sensitivity of cancer cell lines expressing SLFN11 at high levels, but also suggest that SLFN11 expression can serve as a biomarker to predict responses to DNAdamaging therapeutic agents.

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Section: Discussionmentioning

confidence: 96%

SLFN 11 inhibits checkpoint maintenance and homologous recombination repair

et al. 2015

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“…Cells depleted of PrimPol display an increase of spontaneous DNA damage and are defective in restarting stalled replication forks ( Wan et al, 2013 ). Thus, it is believed to be an important player in bypassing DNA lesions and restarting stalled replication ( Im et al, 2013 ). The recruitment of PrimPol to stalled forks seems to be via its direct interaction with the OB-C domain of RPA ( Wan et al, 2013 ).…”

Section: Rpamentioning

confidence: 99%

“…lesions and restarting stalled replication (Im et al, 2013). The recruitment of PrimPol to stalled forks seems to be via its direct interaction with the OB-C domain of RPA (Wan et al, 2013).…”

Section: Rpa In Regulating Activities Of Other Polymerases/helicases mentioning

confidence: 99%

Roles of OB-Fold Proteins in Replication Stress

Nguyen

Kim

Sang

et al. 2020

Front. Cell Dev. Biol.

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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.

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“…It possesses both primase and DNA polymerase activities in vitro and is recruited to sites of DNA damage and stalled replication forks through its direct interaction with RPA1 [57][58][59][60][61][62]. Evidence has indicated that RPA1 binding is required for the cellular function of hPrimol1 in response to DNA replication stress [57][58][59][60][61][62].…”

Section: Rpa and Dna Replicationmentioning

confidence: 99%

“…hPrimpol1 is a recently identified DNA primase-polymerase that is involved in the response to DNA replication stress [54][55][56][57][58][59][60][61][62]. It possesses both primase and DNA polymerase activities in vitro and is recruited to sites of DNA damage and stalled replication forks through its direct interaction with RPA1 [57][58][59][60][61][62].…”

Section: Rpa and Dna Replicationmentioning

confidence: 99%

Replication protein A and more: single-stranded DNA-binding proteins in eukaryotic cells

Liu

Huang

2016

ABBS

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Single-stranded DNA-binding proteins (SSBs) play essential roles in DNA replication, recombinational repair, and maintenance of genome stability. In human, the major SSB, replication protein A (RPA), is a stable heterotrimer composed of subunits of RPA1, RPA2, and RPA3, each of which is conserved not only in mammals but also in all other eukaryotic species. In addition to RPA, other SSBs have also been identified in the human genome, including sensor of single-stranded DNA complexes 1 and 2 (SOSS1/2). In this review, we summarize our current understanding of how these SSBs contribute to the maintenance of genome stability.

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Human Primpol1: a novel guardian of stalled replication forks

Abstract: Huang and colleagues identify a human primase‐polymerase that is required for stalled replication fork restart and the maintenance of genome integrity.

Cited by 7 publications

References 11 publications

SLFN 11 inhibits checkpoint maintenance and homologous recombination repair

SLFN 11 inhibits checkpoint maintenance and homologous recombination repair

Roles of OB-Fold Proteins in Replication Stress

Replication protein A and more: single-stranded DNA-binding proteins in eukaryotic cells

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