FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair.
Fanconi anemia (FA) is caused by mutations in 13 Fanc genes and renders cells hypersensitive to DNA interstrand cross-linking (ICL) agents. A central event in the FA pathway is mono-ubiquitylation of the FANCI-FANCD2 (ID) protein complex. Here, we characterize a previously unrecognized nuclease, Fanconi anemia-associated nuclease 1 (FAN1), that promotes ICL repair in a manner strictly dependent on its ability to accumulate at or near sites of DNA damage and that relies on mono-ubiquitylation of the ID complex. Thus, the mono-ubiquitylated ID complex recruits the downstream repair protein FAN1 and facilitates the repair of DNA interstrand cross-links.
Liu
Ting
T
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Ghosal
Gargi
G
Yuan
Jingsong
J
Chen
Junjie
J
Huang
Jun
J
D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D064251:Multifunctional Enzymes; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination; D016335:Zinc Fingers
C499905:FANCD2 protein, human; C519921:FANCI protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins; D064251:Multifunctional Enzymes; D050505:Mutant Proteins; D057149:Ubiquitinated Proteins; D016685:Mitomycin; D004247:DNA; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C551063:FAN1 protein, human