Faculty Opinions recommendation of The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements.

2002 ◽  
Author(s):  
Stephen Jackson
Keyword(s):  
Double Strand Breaks ◽  
Chromosome Rearrangements ◽  
Strand Breaks ◽  
Mre11 Complex

Structural basis for DNA recognition and nuclease processing by the Mre11 homologue SbcD in double-strand breaks repair

2014 ◽  
Vol 70 (2) ◽  
pp. 299-309 ◽  
Author(s):  
Shun Liu ◽  
Li-fei Tian ◽  
Yan-ping Liu ◽  
Xiao-min An ◽  
Qun Tang ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Catalytic Mechanism ◽  
Double Strand Breaks ◽  
Structural Basis ◽  
State Transitions ◽  
Endonuclease Activity ◽  
High Concentration ◽  
Binding Model ◽  
Strand Breaks ◽  
Mre11 Complex

The Mre11 complex comprising meiotic recombination 11 (Mre11), Rad50 and Nijmegen breakage syndrome 1 (Nbs1) plays multiple important roles in the sensing, processing and repair of DNA double-strand breaks (DSBs). Here, crystal structures of theEscherichia coliMre11 homologue SbcD and its Mn2+complex are reported. Dimerization of SbcD depends on a four-helix bundle consisting of helices α2, α3, α2′ and α3′ of the two monomers, and the irregular and bent conformation of helices α3 and α3′ in the SbcD dimer results in a dimeric arrangement that differs from those of previously reported Mre11 dimers. This finding indicates a distinct selectivity in DNA substrate recognition. The biochemical data combined with the crystal structures revealed that the SbcD monomer exhibits single-stranded DNA (ssDNA) endonuclease activity and double-stranded DNA (dsDNA) exonuclease activity on the addition of a high concentration of Mn2+. For the first time, atomic force microscopy analysis has been used to demonstrate that the SbcD monomer also possesses Mn2+-dependent dsDNA endonuclease activity. Loop β7–α6 of SbcD is likely to be a molecular switch and plays an important role in the regulation of substrate binding, catalytic reaction and state transitions. Based on structural and mutational analyses, a novel ssDNA-binding model of SbcD is proposed, providing insight into the catalytic mechanism of DSBs repair by the Mre11 complex.

scholarly journals NBS1 is required for macrophage homeostasis and functional activity in mice

Blood ◽  
2015 ◽  
Vol 126 (22) ◽  
pp. 2502-2510 ◽  
Author(s):  
Selma Pereira-Lopes ◽  
Juan Tur ◽  
Juan A. Calatayud-Subias ◽  
Jorge Lloberas ◽  
Travis H. Stracker ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Inflammatory Responses ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Hypomorphic Allele ◽  
Mre11 Complex ◽  
Key Points ◽  
Damage Response

Key Points Nbs1 is a component of the MRE11 complex, which is a sensor of DNA double-strand breaks and plays a crucial role in the DNA damage response. In mice with a hypomorphic allele of Nbs1, macrophages exhibit increased senescence and abnormal proliferation and inflammatory responses.

Crossover promotion and prevention

2006 ◽  
Vol 34 (4) ◽  
pp. 537-541 ◽  
Author(s):  
A. Lorenz ◽  
M.C. Whitby
Keyword(s):  
Genetic Diversity ◽  
Homologous Recombination ◽  
Loss Of Heterozygosity ◽  
Chromosome Segregation ◽  
Vegetative Growth ◽  
Double Strand Breaks ◽  
Chromosome Rearrangements ◽  
Crossing Over ◽  
Vegetative Cells ◽  
Strand Breaks

Homologous recombination is an important mechanism for the repair of double-strand breaks in DNA. One possible outcome of such repair is the reciprocal exchange or crossing over of DNA between chromosomes. Crossovers are beneficial during meiosis because, as well as generating genetic diversity, they promote proper chromosome segregation through the establishment of chiasmata. However, crossing over in vegetative cells can potentially result in loss of heterozygosity and chromosome rearrangements, which can be deleterious. Consequently, cells have evolved mechanisms to limit crossing over during vegetative growth while promoting it during meiosis. Here, we provide a brief review of how some of these mechanisms are thought to work.

Repair pathway choice for double-strand breaks

2020 ◽  
Vol 64 (5) ◽  
pp. 765-777 ◽  
Author(s):  
Yixi Xu ◽  
Dongyi Xu
Keyword(s):  
Cell Cycle ◽  
Double Strand Breaks ◽  
Homologous Region ◽  
Gene Repair ◽  
Repair Pathway ◽  
Dna Double Strand Breaks ◽  
Environmental Radiation ◽  
Strand Breaks ◽  
Dna End Resection ◽  
End Resection

Abstract Deoxyribonucleic acid (DNA) is at a constant risk of damage from endogenous substances, environmental radiation, and chemical stressors. DNA double-strand breaks (DSBs) pose a significant threat to genomic integrity and cell survival. There are two major pathways for DSB repair: nonhomologous end-joining (NHEJ) and homologous recombination (HR). The extent of DNA end resection, which determines the length of the 3′ single-stranded DNA (ssDNA) overhang, is the primary factor that determines whether repair is carried out via NHEJ or HR. NHEJ, which does not require a 3′ ssDNA tail, occurs throughout the cell cycle. 53BP1 and the cofactors PTIP or RIF1-shieldin protect the broken DNA end, inhibit long-range end resection and thus promote NHEJ. In contrast, HR mainly occurs during the S/G2 phase and requires DNA end processing to create a 3′ tail that can invade a homologous region, ensuring faithful gene repair. BRCA1 and the cofactors CtIP, EXO1, BLM/DNA2, and the MRE11–RAD50–NBS1 (MRN) complex promote DNA end resection and thus HR. DNA resection is influenced by the cell cycle, the chromatin environment, and the complexity of the DNA end break. Herein, we summarize the key factors involved in repair pathway selection for DSBs and discuss recent related publications.

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