Fanconi-like crosslink repair in yeast.docVIP

DaeeandMyungGenomeIntegrity2012,3:7 /content/3/1/7 GENOME INTEGRITY COMMENTARY OpenAccess Fanconi-likecrosslinkrepairinyeast DanielleLDaeeandKyungjaeMyung* Abstract InterstrandcrosslinkscovalentlylinkcomplementaryDNAstrands,blockreplicationandtranscription,andcantrigger celldeath.Ineukaryoticsystemsseveralpathways,includingtheFanconiAnemiapathway,areinvolvedinrepairing interstrandcrosslinks,buttheirprecisemechanismsremainenigmatic.Thelackoffunctionalhomologsinsimpler modelorganismshassignificantlyhamperedprogressinthisfield.Tworecentstudieshavefinallyidentifieda Fanconi-likeinterstrandcrosslinkrepairpathwayinyeast.Futurestudiesinthissimplisticmodelorganismpromiseto greatlyimproveourbasicunderstandingofcomplexinterstrandcrosslinkrepairpathwaysliketheFanconipathway. Keywords:Fanconianemia,Interstrandcrosslinkrepair,Mph1,Chl1,Slx4,Msh2,Msh6,Mhf1,Mhf2 Background prokaryotic system is relatively well defined. In Escheri- DNA damaging agents such as nitrogen mustard [1,2], chia coli, nucleotide excision repair (NER) creates inci- formaldehyde [3], and cisplatin [4] generate many sions on each side of the ICL. The resulting short lesions that inhibit proper DNA replication and tran- oligonucleotide is attached through the ICL, but is dis- scription. One such lesion, the interstrand crosslink placed from the helix, revealing a gap. The gap is filled (ICL),covalentlylinkstwocomplementaryDNAstrands in by homologous recombination (HR) or translesion and prevents their separation. Importantly, since both bypass synthesis (TLS), and the displaced oligonucleo- strands are damaged, an undamaged template strand is tide/ICLadductisremovedbyNER[12]. not available for repair. Due to these blocks and repair Inlowereukaryotes,defectsinmostknownDNArepair challenges, ICLs are considered one of the most toxic pathways result in ICL sensitivity suggesting that DNA lesions. It is estimated that the presence of just eukaryotic mechanismsare much more complex, involve one un