Linked Life Data

12858174

Source:http://linkedlifedata.com/resource/pubmed/id/12858174

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-8-18
pubmed:abstractText
p53R2, which is regulated by tumor suppressor p53, is a small subunit of ribonucleotide reductase. To determine whether it is involved in DNA repair by supplying deoxyribonucleotides (dNTPs) for resting cells in vivo, we generated a strain of mice lacking Rrm2b (encoding p53R2). These mice developed normally until they were weaned but from then on had growth retardation and early mortality. Pathological examination indicated that multiple organs had failed, and all Rrm2b-null mice died from severe renal failure by the age of 14 weeks. TUNEL staining showed a greater number of apoptotic cells in kidneys of 8-week-old Rrm2b-/- mice relative to wild-type mice. p53 was activated in kidney tissues of Rrm2b-/- mice, leading to transcriptional induction of p53 target genes. Rrm2b-/- mouse embryonic fibroblasts (MEFs) became immortal much earlier than Rrm2b+/+ MEFs. dNTP pools were severely attenuated in Rrm2b-/- MEFs under oxidative stress. Rrm2b deficiency caused higher rates of spontaneous mutation in the kidneys of Rrm2b-/- mice. Our results suggest that p53R2 has a pivotal role in maintaining dNTP levels for repair of DNA in resting cells. Impairment of this pathway may enhance spontaneous mutation frequency and activate p53-dependent apoptotic pathway(s) in vivo, causing severe renal failure, growth retardation and early mortality.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
440-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure through attenuation of dNTP pools.
pubmed:affiliation
Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't