Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links

Research output: Contribution to journalJournal articleResearchpeer-review

Markus Räschle, Godelieve Smeenk, Rebecca K Hansen, Tikira Temu, Yasuyoshi Oka, Marco Y Hein, Nagarjuna Nagaraj, David T Long, Johannes C Walter, Kay Hofmann, Zuzana Storchova, Jürgen Cox, Simon Bekker-Jensen, Niels Mailand, Matthias Mann

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.

Original languageEnglish
Article number1253671
JournalScience (New York, N.Y.)
Volume348
Issue number6234
Pages (from-to)539-
Number of pages10
ISSN0036-8075
DOIs
Publication statusPublished - 1 May 2015

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