Publication Date:
2011-06-11
Description:
The DNA damage response (DDR) is brought about by a protein kinase cascade that orchestrates DNA repair through transcriptional and posttranslational mechanisms. Cell cycle arrest is a hallmark of the DDR. We screened for cells that lacked damage-induced cell cycle arrest and uncovered a critical role for Fanconi anemia and homologous recombination proteins in ATR (ataxia telangiectasia and Rad3-related) signaling. Three DDR candidates, the RNA processing protein INTS7, the circadian transcription factor CLOCK, and a previously uncharacterized protein RHINO, were recruited to sites of DNA damage. RHINO independently bound the Rad9-Rad1-Hus1 complex (9-1-1) and the ATR activator TopBP1. RHINO was recruited to sites of DNA damage by the 9-1-1 complex to promote Chk1 activation. We suggest that RHINO functions together with the 9-1-1 complex and TopBP1 to fully activate ATR.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357496/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357496/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cotta-Ramusino, Cecilia -- McDonald, E Robert 3rd -- Hurov, Kristen -- Sowa, Mathew E -- Harper, J Wade -- Elledge, Stephen J -- R01 AG011085/AG/NIA NIH HHS/ -- R01 GM054137/GM/NIGMS NIH HHS/ -- R37 GM044664/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jun 10;332(6035):1313-7. doi: 10.1126/science.1203430.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard University Medical School, Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21659603" target="_blank"〉PubMed〈/a〉
Keywords:
Ataxia Telangiectasia Mutated Proteins
;
Carrier Proteins/metabolism/*physiology
;
Cell Cycle/genetics
;
Cell Cycle Proteins/*metabolism
;
Cell Line, Tumor
;
Chemokines/genetics/*physiology
;
DNA Damage
;
*DNA Repair
;
DNA-Binding Proteins/metabolism
;
Exonucleases/metabolism
;
Humans
;
Multiprotein Complexes/metabolism
;
Nuclear Proteins/metabolism
;
Protein-Serine-Threonine Kinases/*metabolism
;
*Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
