PMID- 23530069 OWN - NLM STAT- MEDLINE DCOM- 20130523 LR - 20211021 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 201 IP - 1 DP - 2013 Apr 1 TI - FANCJ couples replication past natural fork barriers with maintenance of chromatin structure. PG - 33-48 LID - 10.1083/jcb.201208009 [doi] AB - Defective DNA repair causes Fanconi anemia (FA), a rare childhood cancer-predisposing syndrome. At least 15 genes are known to be mutated in FA; however, their role in DNA repair remains unclear. Here, we show that the FANCJ helicase promotes DNA replication in trans by counteracting fork stalling on replication barriers, such as G4 quadruplex structures. Accordingly, stabilization of G4 quadruplexes in DeltaFANCJ cells restricts fork movements, uncouples leading- and lagging-strand synthesis and generates small single-stranded DNA gaps behind the fork. Unexpectedly, we also discovered that FANCJ suppresses heterochromatin spreading by coupling fork movement through replication barriers with maintenance of chromatin structure. We propose that FANCJ plays an essential role in counteracting chromatin compaction associated with unscheduled replication fork stalling and restart, and suppresses tumorigenesis, at least partially, in this replication-specific manner. FAU - Schwab, Rebekka A AU - Schwab RA AD - The Weatherall Institute of Molecular Medicine, Oxford University, Oxford, England, UK. FAU - Nieminuszczy, Jadwiga AU - Nieminuszczy J FAU - Shin-ya, Kazuo AU - Shin-ya K FAU - Niedzwiedz, Wojciech AU - Niedzwiedz W LA - eng GR - 07-0922/AICR_/Worldwide Cancer Research/United Kingdom GR - G0902418/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130325 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Avian Proteins) RN - 0 (DNA, Single-Stranded) RN - 0 (Heterochromatin) RN - EC 3.6.4.- (DNA Helicases) SB - IM MH - Animals MH - Avian Proteins/genetics/*metabolism MH - Cell Line MH - Chickens MH - DNA Helicases/genetics/*metabolism MH - DNA Repair/*physiology MH - DNA Replication/*physiology MH - DNA, Single-Stranded/genetics/*metabolism MH - Fanconi Anemia/genetics/metabolism MH - Heterochromatin/*enzymology/genetics MH - Humans PMC - PMC3613694 EDAT- 2013/03/27 06:00 MHDA- 2013/05/25 06:00 PMCR- 2013/10/01 CRDT- 2013/03/27 06:00 PHST- 2013/03/27 06:00 [entrez] PHST- 2013/03/27 06:00 [pubmed] PHST- 2013/05/25 06:00 [medline] PHST- 2013/10/01 00:00 [pmc-release] AID - jcb.201208009 [pii] AID - 201208009 [pii] AID - 10.1083/jcb.201208009 [doi] PST - ppublish SO - J Cell Biol. 2013 Apr 1;201(1):33-48. doi: 10.1083/jcb.201208009. Epub 2013 Mar 25.