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Science May 1, 2015; 348 (6234): 1253671.

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

Räschle M , Smeenk G , Hansen RK , Temu T , Oka Y , Hein MY , Nagaraj N , Long DT , Walter JC , Hofmann K , Storchova Z , Cox J , Bekker-Jensen S , Mailand N , Mann M .

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.

PubMed ID: 25931565
PMC ID: PMC5331883
Article link: Science
Grant support: [+]
Genes referenced: rad18 slf1 slf2

References [+] :
Barlow, Identification of early replicating fragile sites that contribute to genome instability. 2013, Pubmed

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