Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links
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Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links. / Räschle, Markus; Smeenk, Godelieve; Hansen, Rebecca K; Temu, Tikira; Oka, Yasuyoshi; Hein, Marco Y; Nagaraj, Nagarjuna; Long, David T; Walter, Johannes C; Hofmann, Kay; Storchova, Zuzana; Cox, Jürgen; Bekker-Jensen, Simon; Mailand, Niels; Mann, Matthias.
In: Science, Vol. 348, No. 6234, 1253671, 2015, p. 539-.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links
AU - Räschle, Markus
AU - Smeenk, Godelieve
AU - Hansen, Rebecca K
AU - Temu, Tikira
AU - Oka, Yasuyoshi
AU - Hein, Marco Y
AU - Nagaraj, Nagarjuna
AU - Long, David T
AU - Walter, Johannes C
AU - Hofmann, Kay
AU - Storchova, Zuzana
AU - Cox, Jürgen
AU - Bekker-Jensen, Simon
AU - Mailand, Niels
AU - Mann, Matthias
N1 - Copyright © 2015, American Association for the Advancement of Science.
PY - 2015
Y1 - 2015
N2 - DNA interstrand cross-links (ICLs) block replication fork progression by inhibiting DNA strand separation. Repair of ICLs requires sequential incisions, translesion DNA synthesis, and homologous recombination, but the full set of factors involved in these transactions remains unknown. We devised a technique called chromatin mass spectrometry (CHROMASS) to study protein recruitment dynamics during perturbed DNA replication in Xenopus egg extracts. Using CHROMASS, we systematically monitored protein assembly and disassembly on ICL-containing chromatin. Among numerous prospective DNA repair factors, we identified SLF1 and SLF2, which form a complex with RAD18 and together define a pathway that suppresses genome instability by recruiting the SMC5/6 cohesion complex to DNA lesions. Our study provides a global analysis of an entire DNA repair pathway and reveals the mechanism of SMC5/6 relocalization to damaged DNA in vertebrate cells.
AB - DNA interstrand cross-links (ICLs) block replication fork progression by inhibiting DNA strand separation. Repair of ICLs requires sequential incisions, translesion DNA synthesis, and homologous recombination, but the full set of factors involved in these transactions remains unknown. We devised a technique called chromatin mass spectrometry (CHROMASS) to study protein recruitment dynamics during perturbed DNA replication in Xenopus egg extracts. Using CHROMASS, we systematically monitored protein assembly and disassembly on ICL-containing chromatin. Among numerous prospective DNA repair factors, we identified SLF1 and SLF2, which form a complex with RAD18 and together define a pathway that suppresses genome instability by recruiting the SMC5/6 cohesion complex to DNA lesions. Our study provides a global analysis of an entire DNA repair pathway and reveals the mechanism of SMC5/6 relocalization to damaged DNA in vertebrate cells.
KW - Animals
KW - Chromatin
KW - DNA Damage
KW - DNA Repair
KW - DNA Repair Enzymes
KW - DNA Replication
KW - DNA-Binding Proteins
KW - Mass Spectrometry
KW - Proteomics
KW - RNA-Binding Proteins
KW - Xenopus
U2 - 10.1126/science.1253671
DO - 10.1126/science.1253671
M3 - Journal article
C2 - 25931565
VL - 348
SP - 539-
JO - Science
JF - Science
SN - 0036-8075
IS - 6234
M1 - 1253671
ER -
ID: 140238644