Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins
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Choreography of the DNA damage response : spatiotemporal relationships among checkpoint and repair proteins. / Lisby, Michael; Barlow, Jacqueline H; Burgess, Rebecca C; Rothstein, Rodney.
In: Cell, Vol. 118, No. 6, 17.09.2004, p. 699-713.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Choreography of the DNA damage response
T2 - spatiotemporal relationships among checkpoint and repair proteins
AU - Lisby, Michael
AU - Barlow, Jacqueline H
AU - Burgess, Rebecca C
AU - Rothstein, Rodney
PY - 2004/9/17
Y1 - 2004/9/17
N2 - DNA repair is an essential process for preserving genome integrity in all organisms. In eukaryotes, recombinational repair is choreographed by multiprotein complexes that are organized into centers (foci). Here, we analyze the cellular response to DNA double-strand breaks (DSBs) and replication stress in Saccharomyces cerevisiae. The Mre11 nuclease and the ATM-related Tel1 kinase are the first proteins detected at DSBs. Next, the Rfa1 single-strand DNA binding protein relocalizes to the break and recruits other key checkpoint proteins. Later and only in S and G2 phase, the homologous recombination machinery assembles at the site. Unlike the response to DSBs, Mre11 and recombination proteins are not recruited to hydroxyurea-stalled replication forks unless the forks collapse. The cellular response to DSBs and DNA replication stress is likely directed by the Mre11 complex detecting and processing DNA ends in conjunction with Sae2 and by RP-A recognizing single-stranded DNA and recruiting additional checkpoint and repair proteins.
AB - DNA repair is an essential process for preserving genome integrity in all organisms. In eukaryotes, recombinational repair is choreographed by multiprotein complexes that are organized into centers (foci). Here, we analyze the cellular response to DNA double-strand breaks (DSBs) and replication stress in Saccharomyces cerevisiae. The Mre11 nuclease and the ATM-related Tel1 kinase are the first proteins detected at DSBs. Next, the Rfa1 single-strand DNA binding protein relocalizes to the break and recruits other key checkpoint proteins. Later and only in S and G2 phase, the homologous recombination machinery assembles at the site. Unlike the response to DSBs, Mre11 and recombination proteins are not recruited to hydroxyurea-stalled replication forks unless the forks collapse. The cellular response to DSBs and DNA replication stress is likely directed by the Mre11 complex detecting and processing DNA ends in conjunction with Sae2 and by RP-A recognizing single-stranded DNA and recruiting additional checkpoint and repair proteins.
KW - Cell Cycle Proteins
KW - DNA
KW - DNA Damage
KW - DNA Repair
KW - DNA-Binding Proteins
KW - Endodeoxyribonucleases
KW - Endonucleases
KW - Exodeoxyribonucleases
KW - Fungal Proteins
KW - G2 Phase
KW - Gamma Rays
KW - Gene Expression Regulation, Fungal
KW - Genes, cdc
KW - Hydroxyurea
KW - Intracellular Signaling Peptides and Proteins
KW - Oxidative Stress
KW - Protein-Serine-Threonine Kinases
KW - Reaction Time
KW - Recombination, Genetic
KW - Replication Protein A
KW - S Phase
KW - Saccharomyces cerevisiae
KW - Saccharomyces cerevisiae Proteins
KW - Time Factors
KW - Transcription Factors
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Research Support, U.S. Gov't, P.H.S.
U2 - 10.1016/j.cell.2004.08.015
DO - 10.1016/j.cell.2004.08.015
M3 - Journal article
C2 - 15369670
VL - 118
SP - 699
EP - 713
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -
ID: 184396364