Biomarker: MRE11

Histology type: endometrial carcinoma

Country: Switzerland

Region: Basel and Zurich

Followed up time :

Subgroup 1 name : negative

Subgroup 1 number: 132

Subgroup 2 name: positive

Subgroup 2 number: 298

Conclusion: MRE11 protein expression using immunohistochemistry could be investigated as a predictive biomarker for PARP-inhibitor treatment.

Sample type : tissue

Sample method: immunohistochemistry 

Expression pattern : Loss( nuclear immunoreactivity was scored as: negative (0) )

Expression elevation: The nuclear immunoreactivity of MRE11, RAD50, and NBS1 was scored as: negative (0), weak (1), moderate (2) and strong (3). The protein expression of the mismatch repair genes was considered as positive when nuclear staining was evident. Stromal cells showing nuclear staining were used as a positive control.

Funtion description: One endometrial cell line showed a markedly reduced MRE11 expression due to a homozygous poly(T) mutation of MRE11, thereby exhibiting an increased sensitivity to BMN673. MRE11 depletion sensitizes MRE11 expressing EC cell lines to the treatment with BMN673. The increased sensitivity to PARP-inhibition correlates with reduced RAD51 foci formation upon ionizing radiation in MRE11-depleted cells.

Funtion Uniprot: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11 (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). RAD50 may be required to bind DNA ends and hold them in close proximity (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289, PubMed:30612738). The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888).

UniProt ID: P49959

UniProt Link: https://www.uniprot.org/uniprotkb/P49959/entry

Biological function from UniProt: #DNA damage #DNA repair #Host-virus interaction #Meiosis

Molecular function from UniProt:

Subcellular UniProt: #Chromosome #Nucleus #Telomere

Alternative name from UniProt:

Miscellaneous: In case of infection by adenovirus E4, the MRN complex is inactivated and degraded by viral oncoproteins, thereby preventing concatenation of viral genomes in infected cells.

Activity regulation: Interaction with SAMHD1 stimulates the double-strand-specific 3'-5' exonuclease activity.

Recommended name: Double-strand break repair protein MRE11

Gene name from HGNC: MRE11 (ATLD, MRE11A)

HPA class: Cancer-related genes Disease related genes Human disease related genes Plasma proteins

AlphaFold DB: P49959

AlphaFold Link: https://www.uniprot.org/uniprotkb/P49959/entry#structure

HPA link: https://www.proteinatlas.org/ENSG00000020922-MRE11

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Ubiquitous nuclear expression.

Single cell type specificity Cell type enhanced (Cytotrophoblasts, Granulosa cells, Alveolar cells type 1, Syncytiotrophoblasts)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Nucleoplasm

Cancer prognostic summary HPA Prognostic marker in liver cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000020922-MRE11/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000020922-MRE11/pathology/endometrial+cancer

Expression figure legend: MRE11 protein expression in endometrial carcinomas as assessed by immunihistochemistry.$ Decrease in MRE11 expression and function leads to increased sensitivity towards PARP inhibition in endometrial carcinoma cell lines.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057395/figure/pone-0100041-g001/$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057395/figure/pone-0100041-g003/

Phenotype ID: 604391

Disease: Ataxia-telangiectasia-like disorder 1 (ATLD1);No disease ID;

Note1: The disease is caused by variants affecting the gene represented in this entry;Defects in MRE11 can be a cause of nephronophthisis-related ciliopathies (NPHP-RC), a group of recessive diseases that affect kidney, retina and brain. A homozygous truncating mutation MRE11 has been found in patients with cerebellar vermis hypoplasia, ataxia and dysarthria;

Note2: A number sign (#) is used with this entry because ataxia-telangiectasia-like disorder-1 (ATLD1) is caused by homozygous or compound heterozygous mutation in the MRE11A gene (MRE11; 600814) on chromosome 11q21.

OMIM: 600814;604391;

OMIM link1: https://www.omim.org/entry/604391

OMIM link2: https://www.omim.org/entry/600814;https://www.omim.org/entry/604391;

Phenotype: Ataxia-telangiectasia-like disorder 1

HGNC ID: HGNC:7230

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7230