Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells.
Yeast Mre11 functions with Rad50 and Xrs2 in a complex that has pivotal roles in homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand break (DSB) repair pathways. Vertebrate Mre11 is essential. Conditionally, MRE11 null chicken DT40 cells accumulate chromosome breaks and die upon Mre11 repression, showing frequent centrosome amplification. Mre11 deficiency also causes increased radiosensitivity and strongly reduced targeted integration frequencies. Mre11 is, therefore, crucial for HR and essential in mitosis through its role in chromosome maintenance by recombinational repair. Surprisingly perhaps, given the role of Mre11 in yeast NHEJ, disruption of NHEJ by deletion of KU70 greatly exacerbates the effects of MRE11 deficiency, revealing a significant Mre11-independent component of metazoan NHEJ.
Yamaguchi-Iwai
Y
Y
Bayer-Chair Department of Molecular Immunology and Allergology, Faculty of Medicine.
Sonoda
E
E
Sasaki
M S
MS
Morrison
C
C
Haraguchi
T
T
Hiraoka
Y
Y
Yamashita
Y M
YM
Yagi
T
T
Takata
M
M
Price
C
C
Kakazu
N
N
Takeda
S
S
D000818:Animals; D030161:Avian Proteins; D001402:B-Lymphocytes / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D018385:Centrosome / Q000502:physiology; D002645:Chickens; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D051135:Rad51 Recombinase; D011995:Recombination, Genetic / Q000235:genetics / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C495150:RAD51 protein, Gallus gallus; D051135:Rad51 Recombinase; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae