Recruitment of RBM6 to DNA Double-Strand Breaks Fosters Homologous Recombination Repair

Awwad, Samah W.; Darawshe, Malak M; Machour, Feras E; Arman, Inbar; Ayoub, Nabieh

doi:10.1080/10985549.2023.2187105

Cited by 5 publications

(5 citation statements)

References 63 publications

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“…While many SFs promote HR by supporting the proper expression of HR factors, some SFs seem to have a direct role in HR, in addition to their canonical function in splicing (Awwad et al, 2023;Prados-Carvajal et al, 2018). We consider that SART1 directly promotes HR because knockdown of this SF did not affect the expression of HR-related factors (Figs.…”

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that many SFs are involved in HR (Adamson et al, 2012; Anantha et al, 2013; Awwad et al, 2023; Herr et al, 2015; MacHour et al, 2021; Marchesini et al, 2017; Onyango et al, 2017; Prados-Carvajal et al, 2018; Savage et al, 2014; Tanikawa et al, 2016). While many SFs promote HR by supporting the proper expression of HR factors, some SFs seem to have a direct role in HR, in addition to their canonical function in splicing (Awwad et al, 2023; Prados-Carvajal et al, 2018). We consider that SART1 directly promotes HR because knockdown of this SF did not affect the expression of HR-related factors (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, two genome-wide screening studies have identified many SFs as factors promoting homologous recombination (HR), which is a major DSB repair pathway (Adamson et al, 2012; Herr et al, 2015). Previous studies have shown that both the splicing-dependent and splicing-independent functions of SFs contribute to HR promotion (Anantha et al, 2013; Awwad et al, 2023; MacHour et al, 2021; Onyango et al, 2017; Prados-Carvajal et al, 2018; Tanikawa et al, 2016). However, the splicing-independent function (i.e., the direct function) of SFs in HR has not been fully studied.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks

Yamauchi,

Kato,

Yasuhara

et al. 2023

Preprint

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Although previous studies have reported that pre-mRNA splicing factors (SFs) are involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), their exact role in promoting HR remains poorly understood. Here, we showed that SART1, an SF upregulated in several types of cancer, promotes DSB end resection, which is an essential step in HR, without affecting the expression of HR factors. In the promotion of resection, SART1 is epistatic with BRCA1, an HR factor known to promote resection. Mechanistically, SART1 cooperates with BRCA1 to counteract the resection blockade posed by 53BP1 and RIF1. Moreover, SART1 is required for recruitment of the HR-promoting portion of BRCA1 to DSBs. Laser microirradiation experiments revealed that SART1 is recruited to DSBs in a BRCA1-dependent manner, and that the arginine/serine (RS)-rich domain is required for SART1 recruitment to DSBs. We also obtained evidence that SART1 is involved in transcription-associated HR together with BRCA1. Furthermore, chromosome analysis demonstrated that SART1 and BRCA1 epistatically suppressed genomic alterations caused by DSB misrepair in the G2 phase. Collectively, these results indicate that SART1 and BRCA1 cooperatively facilitate resection of DSBs arising in transcriptionally active genomic regions, thereby promoting faithful HR repair of such DSBs and suppressing genome instability.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks

Yamauchi,

Kato,

Yasuhara

et al. 2023

Preprint

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“…The elevation of related genes caused many cells to turn from the G1 phase to the S phase. DNA DSBs hindered DNA replication and the cell cycle was arrested in the S phase [ 48 , 49 ]. Through the rescue experiments, we could speculate that the effect of KDM5B on the cell cycle was achieved through MTF1.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of KDM5B Leads to DNA Damage and Cell Cycle Arrest in Granulosa Cells via MTF1

Yang

Cai

Guo

et al. 2023

CIMB

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KDM5B is essential for early embryo development, which is under the control of maternal factors in oocytes. Granulosa cells (GCs) play a critical role during oocyte mature. However, the role of KDM5B in GCs remains to be elucidated. In the current study, we found that KDM5B expressed highly in the ovaries and located in goat GCs. Using an RNA sequence, we identified 1353 differentially expressed genes in the KDM5B knockdown GCs, which were mainly enriched in cell cycle, cell division, DNA replication and the cellular oxidative phosphorylation regulation pathway. Moreover, we reported a decrease in the percentage of proliferated cells but an increase in the percentage of apoptotic cells in the KDM5B knockdown GCs. In addition, in the KDM5B knockdown GCs, the percentage of GCs blocked at the S phase was increased compared to the NC group, suggesting a critical role of KDM5B in the cell cycle. Moreover, in the KDM5B knockdown GCs, the reactive oxygen species level, the mitochondrial depolarization ratio, and the expression of intracellular phosphorylated histone H2AX (γH2AX) increased, suggesting that knockdown of KDM5B leads to DNA damage, primarily in the form of DNA double-strand breaks (DSBs). Interestingly, we found a down-regulation of MTF1 in the KDM5B knockdown GCs, and the level of cell proliferation, as well as the cell cycle block in the S phase, was improved. In contrast, in the group with both KDM5B knockdown and MTF1 overexpression, the level of ROS, the expression of γH2AX and the number of DNA DSB sites decreased. Taken together, our results suggest that KDM5B inhibits DNA damage and promotes the cell cycle in GCs, which might occur through the up-regulation of MTF1.

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Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks

Ozaki,

Kato,

Yasuhara

et al. 2024

Sci Rep

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Recruitment of RBM6 to DNA Double-Strand Breaks Fosters Homologous Recombination Repair

Cited by 5 publications

References 63 publications

Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks

Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks

Knockdown of KDM5B Leads to DNA Damage and Cell Cycle Arrest in Granulosa Cells via MTF1

Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks

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