Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 699-713 |
| Number of pages | 15 |
| Journal | Cell |
| Volume | 118 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 17 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
Choreography of the DNA damage response : Spatiotemporal relationships among checkpoint and repair proteins. / Lisby, Michael; Barlow, Jacqueline; Burgess, Rebecca C.; Rothstein, Rodney.
In: Cell, Vol. 118, No. 6, 17.09.2004, p. 699-713.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Choreography of the DNA damage response
T2 - Spatiotemporal relationships among checkpoint and repair proteins
AU - Lisby, Michael
AU - Barlow, Jacqueline
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.
UR - http://www.scopus.com/inward/record.url?scp=4544281398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4544281398&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2004.08.015
DO - 10.1016/j.cell.2004.08.015
M3 - Article
C2 - 15369670
AN - SCOPUS:4544281398
VL - 118
SP - 699
EP - 713
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -