WRNIP1: A new guardian of genome integrity at stalled replication forks

Leuzzi, Giuseppe; Marabitti, Veronica; Pichierri, Pietro; Franchitto, Annapaola

doi:10.1080/23723556.2016.1215777

Cited by 4 publications

(6 citation statements)

References 11 publications

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“…These data again confirmed that Banp profoundly regulates chromosome segregation during mitosis by directly activating transcription of ncapg and cenpt genes. In addition, wrnip1 is interesting, because it protects stalled replication forks from MRE11-mediated degradation and promotes fork restart after replication stress ( Leuzzi et al, 2016a ; Leuzzi et al, 2016b ). We confirmed that wrnip1 mRNA is normally expressed in retinal progenitor cells in zebrafish and that its expression is reduced in banp rw337 mutants at 48 hpf ( Figure 6—figure supplement 2B ).…”

Section: Resultsmentioning

confidence: 99%

“…Among these eight cell-cycle regulators, interestingly, we identified wrnip1 . WRNIP1 protects stalled replication forks, especially fork reversal, from MRE11- and SLX4-mediated degradation and promotes fork restart by cooperating with BRCA2 to stabilize RAD51 on single-stranded DNA of stalled forks ( Leuzzi et al, 2016a ; Leuzzi et al, 2016b ; Porebski et al, 2019 ). In addition, wrnip1 regulates another fork protection mechanism called damage bypass, consisting of translesion synthesis (TLS) ( Yoshimura et al, 2019 ) and template switching (TS) ( Jiménez-Martín et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Babu

Takeuchi

Masai

2022

eLife

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Btg3-associated nuclear protein (Banp) was originally identified as a nuclear matrix-associated region (MAR)-binding protein and it functions as a tumor suppressor. At the molecular level, Banp regulates transcription of metabolic genes via a CGCG-containing motif called the Banp motif. However, its physiological roles in embryonic development are unknown. Here, we report that Banp is indispensable for the DNA damage response and chromosome segregation during mitosis. Zebrafish banp mutants show mitotic cell accumulation and apoptosis in developing retina. We found that DNA replication stress and tp53-dependent DNA damage responses were activated to induce apoptosis in banp mutants, suggesting that Banp is required for regulation of DNA replication and DNA damage repair. Furthermore, consistent with mitotic cell accumulation, chromosome segregation was not smoothly processed from prometaphase to anaphase in banp morphants, leading to a prolonged M-phase. Our RNA- and ATAC-sequencing identified 31 candidates for direct Banp target genes that carry the Banp motif. Interestingly, a DNA replication fork regulator, wrnip1, and two chromosome segregation regulators, cenpt and ncapg, are included in this list. Thus, Banp directly regulates transcription of wrnip1 for recovery from DNA replication stress, and cenpt and ncapg for chromosome segregation during mitosis. Our findings provide the first in vivo evidence that Banp is required for cell-cycle progression and cell survival by regulating DNA damage responses and chromosome segregation during mitosis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Babu

Takeuchi

Masai

2022

eLife

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show abstract

“…These data again confirmed that Banp profoundly regulates chromosome segregation during mitosis by directly activating transcription of ncapg and cenpt genes. In addition, wrnip1 is interesting, because it protects stalled replication forks from MRE11-mediated degradation and promotes fork restart after replication stress (Leuzzi et al, 2016a; Leuzzi et al, 2016b). We confirmed that wrnip1 mRNA is normally expressed in retinal progenitor cells in zebrafish and that its expression is reduced in banp rw337 mutants at 48 hpf (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These data suggest that Banp is required to maintain wrnip1 mRNA expression in retinal progenitor cells in zebrafish. Loss of wrnip1 is expected to cause genomic instability due to excessive fork degradation (Leuzzi et al, 2016b). So, the reduction of wrnip1 mRNA expression may explain the significant accumulation of γ- H2AX+ retinal cells in banp rw337 mutants (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Among these eight cell- cycle regulators, interestingly, we identified wrnip1 . WRNIP1 protects stalled replication forks, especially fork reversal, from MRE11- and SLX4-mediated degradation and promotes fork restart by cooperating with BRCA2 to stabilize RAD51 on single-stranded DNA of stalled forks (Leuzzi et al, 2016a; Leuzzi et al, 2016b; Porebski et al, 2019). In addition, wrnip1 regulates another fork protection mechanism called damage bypass, consisting of translesion synthesis (TLS) (Yoshimura et al, 2019) and template switching (TS) (Jimenez-Martin et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Babu

Takeuchi

Masai

2021

Preprint

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Btg3-associated nuclear protein (Banp) was originally identified as a nuclear matrix-associated protein and it functions as a tumor suppressor. At molecular level, Banp regulates transcription of metabolic genes via a CGCG-containing motif called the Banp motif. However, its physiological roles in embryonic development are unknown. Here we report that Banp is indispensable for DNA damage response and chromosome segregation during mitosis. Zebrafish banp mutants show mitotic arrest and apoptosis in developing retina. We found that DNA replication stress and tp53-dependent DNA damage responses were activated to induce apoptosis in banp mutants, suggesting that Banp is required for integrity of DNA replication and DNA damage repair. Furthermore, in banp mutants, chromosome segregation was not smoothly processed from prometaphase to anaphase, leading to a prolonged M-phase. Our RNA- and ATAC-sequencing identified 31 candidates for direct Banp target genes that carry the Banp motif. Interestingly, two chromosome segregation regulators, cenpt and ncapg, are included in this list. Thus, Banp directly regulates transcription of cenpt and ncapg to promote chromosome segregation during mitosis. Our findings provide the first in vivo evidence that Banp is required for cell-cycle progression and cell survival by regulating DNA damage responses and chromosome segregation during mitosis.

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Werner helicase interacting protein 1 contributes to G-quadruplex processing in human cells

Hegedus,

Toth,

Harami

et al. 2024

Sci Rep

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Genome replication is frequently impeded by highly stable DNA secondary structures, including G-quadruplex (G4) DNA, that can hinder the progression of the replication fork. Human WRNIP1 (Werner helicase Interacting Protein 1) associates with various components of the replication machinery and plays a crucial role in genome maintenance processes. However, its detailed function is still not fully understood. Here we show that human WRNIP1 interacts with G4 structures and provide evidence for its contribution to G4 processing. The absence of WRNIP1 results in elevated levels of G4 structures, DNA damage and chromosome aberrations following treatment with PhenDC3, a G4-stabilizing ligand. Additionally, we establish a functional and physical relationship between WRNIP1 and the PIF1 helicase in G4 processing. In summary, our results suggest that WRNIP1 aids genome replication and maintenance by regulating G4 processing and this activity relies on Pif1 DNA helicase.

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WRNIP1: A new guardian of genome integrity at stalled replication forks

Cited by 4 publications

References 11 publications

Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Werner helicase interacting protein 1 contributes to G-quadruplex processing in human cells

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