Recombinant Human Mre11 protein (GST tag N-Terminus)

Specifications

Form

Liquid

General info

Function

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).. MRE11 contains two DNA-binding domains (DBDs), enabling it to bind both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA).

Sequence similarities

Belongs to the MRE11/RAD32 family.

Post-translational modifications

Phosphorylated by ATM at Ser-676 and Ser-678 in response to DNA damage, promoting MRE11 activity: phosphorylation activates MRE11 by preventing the interaction between MRE11 and the C1QBP inhibitor (PubMed:16601701, PubMed:26240375, PubMed:31353207). Phosphorylation at Ser-649 by PLK1 primes for phosphorylation at Ser-688 by CK2, inhibiting recruitment of the MRN complex to DNA damage sites (PubMed:28512243).. Asymmetric dimethylation by PRMT1 promotes MRE11 exonuclease activity.. Lactylation at Lys-673 by CREBBP/CBP in response to DNA damage promotes DNA binding and MRE11 activity.. Acetylated on lysine residues by KAT2A /GCN5.. Ubiquitinated following DNA damage (PubMed:30612738). Ubiquitination triggers interaction with UBQLN4, leading to MRE11 removal from chromatin and degradation by the proteasome (PubMed:30612738). Ubiquitinated at Lys-339 and Lys-480 by RNF126 via 'Lys-27'- and 'Lys-29'-linked polyubiquitin chains, promoting the exonuclease activity of MRE11 (PubMed:36563124).. SUMOylated by PIAS1, stabilizing MRE11 on chromatin during end resection (PubMed:36050397). DeSUMOylated by SENP3 following removal from DNA double-strand breaks (DSBs) (PubMed:36050397).. Ufmylation at Lys-282 promotes MRE11 activity and is required for activation of the ATM and ATR kinases by the MRN complex.. (Microbial infection) Following infection by adenovirus E4, ubiquitinated and degraded by a SCF-like E3 ubiquitin ligase complex containing viral proteins E1B-55K and E4-ORF6.