MRE11

Chr 11q21

MRE11 double strand break repair nuclease

Aliases:: ATLD
MANE:: ENST00000323929.8

OMIM: 600814 ↗NCBI: 4361 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

MRE11 · P49959

v62025-08-01

Predicted Aligned Error matrix for MRE11 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

75.4/ 100

Confident

708 residues

Confidence breakdown

Very high(≥ 90)48%
Confident(70–90)20%
Low(50–70)5%
Very low(< 50)28%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Ataxia and cerebellar anomalies - narrow panel
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia
BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood
BIALLELIC, autosomal or pseudoautosomal
COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel
BIALLELIC, autosomal or pseudoautosomal

+9 more panels — install the extension to see the full list inline on any page.

Disease associations (Open Targets)

ataxia-telangiectasia-like disorder
0.83
hereditary neoplastic syndrome
0.57
Inherited cancer-predisposing syndrome
0.57
cancer
0.55
Hereditary breast and ovarian cancer syndrome
0.51
hereditary breast ovarian cancer syndrome
0.51
breast carcinoma
0.41
Nijmegen breakage syndrome-like disorder
0.37
colonic neoplasm
0.34
triple-negative breast carcinoma
0.33

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Double-strand break repair protein MRE11

Core 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:11741547, PubMed:14657032, PubMed:22078559, PubMed:23080121, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:28867292, PubMed:29670289, PubMed:30464262, PubMed:30612738, PubMed:31353207, PubMed:37696958, PubMed:38128537, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:24316220, PubMed:28867292, PubMed:31353207, PubMed:38128537). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:24316220, PubMed:27889449, PubMed:28867292, PubMed:36050397, PubMed:38128537). Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity (PubMed:11741547, PubMed:22078559, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:29670289, PubMed:31353207, PubMed:36563124, PubMed:9590181, PubMed:9651580, PubMed:9705271). After DSBs, MRE11 is loaded onto DSBs sites and cleaves DNA by cooperating with RBBP8/CtIP to initiate end resection (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 first endonucleolytically cleaves the 5' strand at DNA DSB ends to prevent non-homologous end joining (NHEJ) and licence HR (PubMed:24316220). It then generates a single-stranded DNA gap via 3' to 5' exonucleolytic degradation to create entry sites for EXO1- and DNA2-mediated 5' to 3' long-range resection, which is required for single-strand invasion and recombination (PubMed:24316220, PubMed:28867292). RBBP8/CtIP specifically promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 endonuclease activity is also enhanced by AGER/RAGE (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:14657032, PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). The MRN complex is involved in the activation of the cGAS-STING pathway induced by DNA damage during tumorigenesis: the MRN complex acts by displacing CGAS from nucleosome sequestration, thereby activating it (By similarity). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888)