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The hSSB1 orthologue Obfc2b is essential for skeletogenesis but dispensable for the DNA damage response in vivo
by
Ferretti, Elisabetta
, Selleri, Licia
, Deroubaix, Stephanie
, Nussenzweig, Michel C
, Robbiani, Davide F
, Feldhahn, Niklas
, Nussenzweig, Andre
, Callen, Elsa
in
Accumulation
/ Animals
/ Apoptosis
/ Apoptosis - genetics
/ B-Lymphocytes - metabolism
/ Bone and Bones - abnormalities
/ Bone and Bones - embryology
/ Cell Division
/ Chondrocytes - metabolism
/ Deoxyribonucleic acid
/ DNA
/ DNA Damage
/ DNA damage response
/ DNA Repair - genetics
/ DNA Replication
/ DNA-Binding Proteins - biosynthesis
/ DNA-Binding Proteins - deficiency
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - physiology
/ EMBO11
/ EMBO13
/ Embryonic growth stage
/ Fibroblasts - metabolism
/ Gene Expression Regulation, Developmental
/ Genes, Lethal
/ Genes, p53
/ Genomics
/ Histones - metabolism
/ hSSB1
/ Humans
/ Lymphocytes
/ Mesoderm - abnormalities
/ Mice
/ Mice, Knockout
/ Mitochondrial Proteins - deficiency
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - physiology
/ Molecular biology
/ Obfc2b
/ Organ Specificity
/ Osteoblasts - metabolism
/ Osteoclasts - metabolism
/ Osteogenesis - genetics
/ Proteins
/ skeletogenesis
2012
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The hSSB1 orthologue Obfc2b is essential for skeletogenesis but dispensable for the DNA damage response in vivo
by
Ferretti, Elisabetta
, Selleri, Licia
, Deroubaix, Stephanie
, Nussenzweig, Michel C
, Robbiani, Davide F
, Feldhahn, Niklas
, Nussenzweig, Andre
, Callen, Elsa
in
Accumulation
/ Animals
/ Apoptosis
/ Apoptosis - genetics
/ B-Lymphocytes - metabolism
/ Bone and Bones - abnormalities
/ Bone and Bones - embryology
/ Cell Division
/ Chondrocytes - metabolism
/ Deoxyribonucleic acid
/ DNA
/ DNA Damage
/ DNA damage response
/ DNA Repair - genetics
/ DNA Replication
/ DNA-Binding Proteins - biosynthesis
/ DNA-Binding Proteins - deficiency
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - physiology
/ EMBO11
/ EMBO13
/ Embryonic growth stage
/ Fibroblasts - metabolism
/ Gene Expression Regulation, Developmental
/ Genes, Lethal
/ Genes, p53
/ Genomics
/ Histones - metabolism
/ hSSB1
/ Humans
/ Lymphocytes
/ Mesoderm - abnormalities
/ Mice
/ Mice, Knockout
/ Mitochondrial Proteins - deficiency
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - physiology
/ Molecular biology
/ Obfc2b
/ Organ Specificity
/ Osteoblasts - metabolism
/ Osteoclasts - metabolism
/ Osteogenesis - genetics
/ Proteins
/ skeletogenesis
2012
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The hSSB1 orthologue Obfc2b is essential for skeletogenesis but dispensable for the DNA damage response in vivo
by
Ferretti, Elisabetta
, Selleri, Licia
, Deroubaix, Stephanie
, Nussenzweig, Michel C
, Robbiani, Davide F
, Feldhahn, Niklas
, Nussenzweig, Andre
, Callen, Elsa
in
Accumulation
/ Animals
/ Apoptosis
/ Apoptosis - genetics
/ B-Lymphocytes - metabolism
/ Bone and Bones - abnormalities
/ Bone and Bones - embryology
/ Cell Division
/ Chondrocytes - metabolism
/ Deoxyribonucleic acid
/ DNA
/ DNA Damage
/ DNA damage response
/ DNA Repair - genetics
/ DNA Replication
/ DNA-Binding Proteins - biosynthesis
/ DNA-Binding Proteins - deficiency
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - physiology
/ EMBO11
/ EMBO13
/ Embryonic growth stage
/ Fibroblasts - metabolism
/ Gene Expression Regulation, Developmental
/ Genes, Lethal
/ Genes, p53
/ Genomics
/ Histones - metabolism
/ hSSB1
/ Humans
/ Lymphocytes
/ Mesoderm - abnormalities
/ Mice
/ Mice, Knockout
/ Mitochondrial Proteins - deficiency
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - physiology
/ Molecular biology
/ Obfc2b
/ Organ Specificity
/ Osteoblasts - metabolism
/ Osteoclasts - metabolism
/ Osteogenesis - genetics
/ Proteins
/ skeletogenesis
2012
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The hSSB1 orthologue Obfc2b is essential for skeletogenesis but dispensable for the DNA damage response in vivo
Journal Article
The hSSB1 orthologue Obfc2b is essential for skeletogenesis but dispensable for the DNA damage response in vivo
2012
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Overview
Human single‐stranded DNA‐binding protein 1 (hSSB1), encoded by
OBFC2B
, was recently characterized as an essential factor for the initiation of DNA damage checkpoints and the maintenance of genomic stability. Here, we report that loss of
Obfc2b
in mice results in perinatal lethality characterized by growth delay and skeletal abnormalities. These abnormalities are associated with accumulation of γH2ax, apoptosis and defective pre‐cartilage condensation, which is essential for normal bone formation. However, deficiency of
Obfc2b
does not affect the initiation of DNA damage checkpoints, Atm activation, or the maintenance of genomic stability in B lymphocytes and primary fibroblasts. Loss of
Obfc2b
results in increased expression of its homologue
Obfc2a
(
hSSB2
). In contrast to
Obfc2b
deficiency, depletion of Obfc2a in fibroblasts results in impaired proliferation, accumulation of γH2ax and increased genomic instability. Thus, the
hSSB1
orthologue
Obfc2b
has a unique function during embryogenesis limited to cell types that contribute to bone formation. While being dispensable in most other cell lineages, its absence leads to a compensatory increase in Obfc2a protein, a homologue required for the maintenance of genomic integrity.
SSB1, a recently identified single‐strand binding protein proposed as a master regulator of DNA damage responses in human cells, plays no genome maintenance roles in mice.
Publisher
John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ Animals
/ Bone and Bones - abnormalities
/ DNA
/ DNA-Binding Proteins - biosynthesis
/ DNA-Binding Proteins - deficiency
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - physiology
/ EMBO11
/ EMBO13
/ Gene Expression Regulation, Developmental
/ Genomics
/ hSSB1
/ Humans
/ Mice
/ Mitochondrial Proteins - deficiency
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - physiology
/ Obfc2b
/ Proteins
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