3t1i
From Proteopedia
Crystal Structure of Human Mre11: Understanding Tumorigenic Mutations
Structural highlights
Disease[MRE11_HUMAN] Hereditary breast and ovarian cancer syndrome;Ataxia-telangiectasia-like disorder. The disease is caused by mutations affecting the gene represented in this entry. Defects in MRE11A 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 MRE11A has been found in patients with cerebellar vermis hypoplasia, ataxia and dysarthria. Function[MRE11_HUMAN] Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. 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 MRE11A to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation. Publication Abstract from PubMedMre11 plays an important role in repairing damaged DNA by cleaving broken ends and by providing a platform for other DNA repair proteins. Various Mre11 mutations have been identified in several types of cancer. We have determined the crystal structure of the human Mre11 core (hMre11), which contains the nuclease and capping domains. hMre11 dimerizes through the interfaces between loop beta3-alpha3 from one Mre11 and loop beta4-beta5 from another Mre11, and between loop alpha2-beta3 from one Mre11 and helices alpha2 and alpha3 from another Mre11, and assembles into a completely different dimeric architecture compared with bacterial or archaeal Mre11 homologs. Nbs1 binds to the region containing loop alpha2-beta3 which participates in dimerization. The hMre11 structure in conjunction with biochemical analyses reveals that many tumorigenic mutations are primarily associated with Nbs1 binding and partly with nuclease activities, providing a framework for understanding how mutations inactivate Mre11. Crystal structure of human mre11: understanding tumorigenic mutations.,Park YB, Chae J, Kim YC, Cho Y Structure. 2011 Nov 9;19(11):1591-602. PMID:22078559[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Chae, J | Cho, Y | Kim, Y | Park, Y B | Dna repair | Endonuclease | Exonuclease | Hydrolase | Metallophosphatase | Mrn complex | Nbs1 | Rad50
