PMID- 18805090 OWN - NLM STAT- MEDLINE DCOM- 20081009 LR - 20220330 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 134 IP - 6 DP - 2008 Sep 19 TI - Mechanism of replication-coupled DNA interstrand crosslink repair. PG - 969-80 LID - 10.1016/j.cell.2008.08.030 [doi] AB - DNA interstrand crosslinks (ICLs) are toxic DNA lesions whose repair occurs in the S phase of metazoans via an unknown mechanism. Here, we describe a cell-free system based on Xenopus egg extracts that supports ICL repair. During DNA replication of a plasmid containing a site-specific ICL, two replication forks converge on the crosslink. Subsequent lesion bypass involves advance of a nascent leading strand to within one nucleotide of the ICL, followed by incisions, translesion DNA synthesis, and extension of the nascent strand beyond the lesion. Immunodepletion experiments suggest that extension requires DNA polymerase zeta. Ultimately, a significant portion of the input DNA is fully repaired, but not if DNA replication is blocked. Our experiments establish a mechanism for ICL repair that reveals how this process is coupled to DNA replication. FAU - Raschle, Markus AU - Raschle M AD - Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Boston, MA 02115, USA. FAU - Knipscheer, Puck AU - Knipscheer P FAU - Enoiu, Milica AU - Enoiu M FAU - Angelov, Todor AU - Angelov T FAU - Sun, Jingchuan AU - Sun J FAU - Griffith, Jack D AU - Griffith JD FAU - Ellenberger, Tom E AU - Ellenberger TE FAU - Scharer, Orlando D AU - Scharer OD FAU - Walter, Johannes C AU - Walter JC LA - eng GR - GM62267/GM/NIGMS NIH HHS/United States GR - R01 GM062267-07/GM/NIGMS NIH HHS/United States GR - R01 GM062267-08/GM/NIGMS NIH HHS/United States GR - R01 GM062267/GM/NIGMS NIH HHS/United States GR - GM55390/GM/NIGMS NIH HHS/United States GR - GM31819/GM/NIGMS NIH HHS/United States GR - R01 GM031819/GM/NIGMS NIH HHS/United States GR - R01 GM055390/GM/NIGMS NIH HHS/United States GR - R01 GM062267-06/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 RN - 9007-49-2 (DNA) RN - EC 2.7.7.- (DNA polymerase zeta) RN - EC 2.7.7.7 (DNA-Directed DNA Polymerase) SB - IM EIN - Cell.2009 May 29;137(5):972. Knipsheer, Puck [corrected to Knipscheer, Puck] MH - Animals MH - Cell-Free System MH - DNA MH - *DNA Repair MH - *DNA Replication MH - DNA-Directed DNA Polymerase/genetics/metabolism MH - Plasmids/genetics/metabolism MH - Xenopus PMC - PMC2748255 MID - NIHMS70634 EDAT- 2008/09/23 09:00 MHDA- 2008/10/10 09:00 PMCR- 2009/09/22 CRDT- 2008/09/23 09:00 PHST- 2007/12/18 00:00 [received] PHST- 2008/07/07 00:00 [revised] PHST- 2008/08/14 00:00 [accepted] PHST- 2008/09/23 09:00 [pubmed] PHST- 2008/10/10 09:00 [medline] PHST- 2008/09/23 09:00 [entrez] PHST- 2009/09/22 00:00 [pmc-release] AID - S0092-8674(08)01075-1 [pii] AID - 10.1016/j.cell.2008.08.030 [doi] PST - ppublish SO - Cell. 2008 Sep 19;134(6):969-80. doi: 10.1016/j.cell.2008.08.030.