MRE11-RAD50-NBS1-CtIP: one key nuclease ensemble functions in the maintenance of genome stability

Zhang, Tao; Zhou, Zenan; Yang, Han; Wang, Weibin

doi:10.1007/s42764-022-00065-2

Cited by 2 publications

(2 citation statements)

References 87 publications

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“…R‐loops have emerged as key players in the development of various cancers [20]. In this study, we provide the first evidence for the interaction between WDR61 and R‐loop using PLA (Fig.…”

Section: Discussionmentioning

confidence: 62%

WDR61 ablation triggers R‐loop accumulation and suppresses breast cancer progression

Hou,

Zhang,

Liu

et al. 2024

The FEBS Journal

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Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen‐induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony‐forming capacity. Further investigations demonstrate that the protective effect of WDR61 loss on breast tumor development is due to genomic instability. Mechanistic studies reveal that WDR61 interacts with the R‐loop, and loss of WDR61 leads to R‐loops accumulation in breast tumor cells, causing DNA damage and subsequent inhibition of cell proliferation. In summary, this study highlights the critical dependence of breast tumors on WDR61, which suppresses R‐loop and counteracts endogenous DNA damage in tumor cells.

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Section: Discussionmentioning

confidence: 62%

WDR61 ablation triggers R‐loop accumulation and suppresses breast cancer progression

Hou,

Zhang,

Liu

et al. 2024

The FEBS Journal

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“…An important interacting partner of NBN is CtIP protein, a fourth eukaryotic, non-catalytic MRN complex subunit, which is essential for the initiation of DNA ends resection. The CtIP is retained at the break site by phosphorylation-dependent binding to the FHA and BRCT domains of the NBN [ 27 , 46 , 47 ].…”

Section: Structure Of the Mrn Complexmentioning

confidence: 99%

Importance of Germline and Somatic Alterations in Human MRE11, RAD50, and NBN Genes Coding for MRN Complex

Stastna

Volková

Soukupová

et al. 2023

IJMS

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The MRE11, RAD50, and NBN genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. Heterozygous germline alterations in the MRN complex genes have been associated with a poorly-specified predisposition to various cancer types. Somatic alterations in the MRN complex genes may represent valuable predictive and prognostic biomarkers in cancer patients. MRN complex genes have been targeted in several next-generation sequencing panels for cancer and neurological disorders, but interpretation of the identified alterations is challenging due to the complexity of MRN complex function in the DNA damage response. In this review, we outline the structural characteristics of the MRE11, RAD50 and NBN proteins, the assembly and functions of the MRN complex from the perspective of clinical interpretation of germline and somatic alterations in the MRE11, RAD50 and NBN genes.

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MRE11-RAD50-NBS1-CtIP: one key nuclease ensemble functions in the maintenance of genome stability

Cited by 2 publications

References 87 publications

WDR61 ablation triggers R‐loop accumulation and suppresses breast cancer progression

WDR61 ablation triggers R‐loop accumulation and suppresses breast cancer progression

Importance of Germline and Somatic Alterations in Human MRE11, RAD50, and NBN Genes Coding for MRN Complex

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