Assessing the link between BACH1/FANCJ and MLH1 in DNA crosslink repair.
FANCJ (also known as BRIP1 or BACH1) is a DNA helicase that was originally identified by its direct interaction with the hereditary breast cancer protein, BRCA1. Similar to BRCA1, FANCJ function is essential for DNA repair and breast cancer suppression. FANCJ is also mutated in the cancer prone syndrome Fanconi anemia, for which patient cells are characterized by extreme sensitivity to agents that generate DNA interstand crosslinks. Unexpectedly, correction of the interstrand crosslink sensitivity of FANCJ-null patient cells did not require the FANCJ/BRCA1 interaction. Instead, FANCJ binding to the mismatch repair protein, MLH1 was required. Given this finding, we address the role of FANCJ and MLH1 in DNA crosslink processing and how their functions could be linked in checkpoint and/or recombination pathways. We speculate that after DNA crosslink processing and repair, the FANCJ/MLH1 interaction is critical for recovery and restart of replication. These ideas are considered and summarized in this review.
Cantor
Sharon B
SB
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. Sharon.Cantor@umassmed.edu
Xie
Jenny
J
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C102108:BACH1 protein, human; D019313:BRCA1 Protein; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1