Rad50 is involved in DNA double-strand break repair (DSBR). The Rad50/Mre11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific 3'-5' exonuclease activity. Rad50 provides an ATP-dependent control of Mre11 by unwinding and/or repositioning DNA ends into the Mre11 active site []. This entry represents Rad50 from archaea and some bacteria.
RAD50 is involved in DNA double-strand break repair (DSBR), telomere maintenance and meiotic recombination [, , ]. The RAD50/MRE11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific exonuclease activity [, ]. RAD50 provides ATP-dependent control of Mre11 by unwinding and/or repositioning DNA ends into the MRE11 active site [, , ]. This entry represents the eukaryotic Rad50 that is distantly related to the SbcC family of bacterial proteins.In Saccharomyces cerevisiae, Rad50 forms the MRX complex with Mre11 and Xrs2. In humans, RAD50 forms the MRN complex with MRE11 and NBN (also known as NBS1). Mutations in the RAD50 gene cause the Nijmegen breakage syndrome-like disorder (NBSLD) []. The genetic variations in the RAD50 gene have been linked to susceptibility to asthma [].
The Mre11 complex is a multi-subunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2, and is involved in checkpoint signalling and DNA replication []. Mre11 has an intrinsic DNA-binding activity that is stimulated by Rad50 on its own or in combination with Nbs1 [].
The Mre11 complex is a multi-subunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2, and is involved in checkpoint signalling and DNA replication []. Mre11 has an intrinsic DNA-binding activity that is stimulated by Rad50 on its own or in combination with Nbs1 [].Mre11 dimerizes via phosphodiesterase domains flanked by a alpha/beta capping domain, process which creates a U-shaped particle with a broad DNA/Rad50 binding cleft []. This superfamily represents the Mre11 capping domain.
The catalytic domains of Rad50 are similar to the ATP-binding cassette of ABC transporters, but are not associated with membrane-spanning domains. The conserved ATP-binding motifs common to Rad50 and the ABC transporter family include the Walker A and Walker B motifs, the Q loop, a histidine residue in the switch region, a D-loop, and a conserved LSGG sequence. This conserved sequence, LSGG, is the most specific and characteristic motif of this family and is thus known as the ABC signature sequence [].
This AAA domain is found in a group of uncharacterised proteins, including YhaN from Bacillus subtilis and DNA double-strand break repair Rad50 ATPase from Archaeoglobus fulgidus.AAA ATPases belong to the AAA+ superfamily of ringshaped P-loop NTPases, which exert their activity through the energy-dependent unfolding of macromolecules [].
Mre11 and Rad50 are two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae. Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50 []. These eukaryotic proteins contain one metallo-phosphoesterase domain followed by an Mre11 DNA-binding domain. S. cerevisiae Mre11 is required for DNA repair and meiosis-specificdouble-strand break (DSB) formation []and has both 3' to 5' exonuclease activity (whichincreases when in complex with Rad50) and endonuclease activity. The N-terminal phosphoesterase domain isrequired for DSB repair, and the carboxyl-terminal dsDNA-binding domain is essential during meiosis forchromatin modification and DSB formation []. Schizosaccharomyces pombe rad32 is required for repair of double strand breaks and recombination [].
This entry represents a small group of nuclease SbcCD subunit C (SbcC) proteins, mainly from gammaproteobacteria. SbcC are known are part of an exonuclease complex with sbcD homologues. SbcCD cleaves DNA hairpin structures. These structures can inhibit DNA replication and are intermediates in certain DNA recombination reactions. The complex acts as a 3'->5' double strand exonuclease that can open hairpins. It also has a 5' single-strand endonuclease activity [].The entry also includes a small number of proteins annotated as probable DNA double-strand break repair Rad50 ATPase, but which are experimentally uncharacterised.
The MRN complex (Mre11-Rad50-Nbs1) plays an important role in many DNA metabolic events that involve DNA double-stranded breaks. MRN is one of the first factors to be localised to DNA lesions where it might have a structural role by tethering and stabilising broken chromosomes [, ]. Rad50 is a split ABC-type ATPase; its centre contains a long heptad repeat that folds into an antiparallel coiled coil, bringing the N-terminal (Walker A) and the C-terminal (Walker B) domains in close proximity []. The apex of the coiled coil contains a dimerization interface, a conserved Cys-X-X-Cys motif in a hook-shaped domain that dimerizes with a second hook domain via cysteine-mediated zinc ion coordination. This zinc dependent dimerization event allows the formation of a complex that has appropriate lengths and conformational proporties to link sister chromatids in homologous recombination and DNA ends in non-homologous end-joining.
This entry includes RINT-1 from animals, Tip20 from yeasts and MAIGO2 (Mag2) from plants. They play a role in anterograde transport from the endoplasmic reticulum (ER) to the Golgi and/or retrograde transport from the Golgi to the ER share sequence similarity []. They are part of the CATCHR (complexes associated with tethering containing helical rods) family which comprises the exocyst, COG, GARP, and DSL1 complexes and share a similar structure organisation with an N-terminal coiled-coil and a C-terminal α-helical bundle, which might be a protein-protein interaction module necessary for the formation of functional complexes.RINT-1 interacts with Rad50 only during late S and G2/M phases and participates in radiation induced checkpoint control []. RINT-1 also functions in membrane trafficking from the endoplasmic reticulum (ER) to the Golgi complex in interphase cells [, , ].Tip20 is involved in the retrograde transport from the Golgi to the ER [, ].Arabidopsis Mag2 functions in the transport of storage protein precursors between the ER and Golgi complex in plants [, ].
