Daee DL, Ferrari E, Longerich S, Zheng XF, Xue X, Branzei D, Sung P, Myung K

Interstrand crosslinks (ICLs) covalently link complementary DNA strands, block DNA replication and transcription, and must be removed to allow cell survival. Several pathways, including the Fanconi Anemia (FA) pathway, can faithfully repair ICLs and maintain genomic integrity; however the precise mechanisms of most ICL repair processes remain enigmatic. In this ...

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study, we genetically characterized a conserved yeast ICL repair pathway comprised of the yeast homologs (Mph1, Chl1, Mhf1, Mhf2) of four FA proteins (FANCM, FANCJ, MHF1, MHF2). This pathway is epistatic with Rad5-mediated DNA damage bypass and distinct from the ICL repair pathways mediated by Rad18 and Pso2. In addition, consistent with FANCM role in stabilizing ICL-stalled replication forks, we present evidence that Mph1 prevents ICL-stalled replication forks from collapsing into double strand breaks (DSBs). This unique repair function of Mph1 is specific for ICL damage and does not extend to other types of damage. These studies reveal the functional conservation of the FA pathway and validate the yeast model for future studies to further elucidate the mechanism of the FA pathway.

Date: Jun. 12, 2012

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