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 -