Abstract
Human exonuclease 1 (EXO1), a 5′→3′ exonuclease, contributes to the regulation of the cell cycle checkpoints, replication fork maintenance, and post replicative DNA repair pathways. These processes are required for the resolution of stalled or blocked DNA replication that can lead to replication stress and potential collapse of the replication fork. Failure to restart the DNA replication process can result in double-strand breaks, cell-cycle arrest, cell death, or cellular transformation. In this review, we summarize the involvement of EXO1 in the replication, DNA repair pathways, cell cycle checkpoints, and the link between EXO1 and cancer.
Highlights
Human exonuclease 1 (EXO1) contributes to checkpoint progression and to several DNA repair pathways involved in reducing DNA replication stress, for example, in mismatch repair (MMR), translesion DNA synthesis (TLS), nucleotide excision repair (NER), double-strand break repair (DSBR), and checkpoint activation to restart stalled DNA forks [1,2,3,4,5,6]
The combined helicase and physical interaction of EXO1 with RECQL1 or WRN may play an important role in the enhancement of DNA strand displacement, such as that occurring during lagging strand DNA synthesis at the replication fork, or during the DNA repair that potentially leads to strand displacement
EXO1 is a central player in DNA metabolic processes
Summary
Human exonuclease 1 (EXO1) contributes to checkpoint progression and to several DNA repair pathways involved in reducing DNA replication stress, for example, in mismatch repair (MMR), translesion DNA synthesis (TLS), nucleotide excision repair (NER), double-strand break repair (DSBR), and checkpoint activation to restart stalled DNA forks [1,2,3,4,5,6]. This suggests significant overlap in the functionality of these enzymes Both human FEN1 and EXO1 have weak flap activity at long 5’ flap overhangs (5–20 nucleotides), but efficiently remove mono- or dinucleotide overhangs [8,11,15]. The combined helicase and physical interaction of EXO1 with RECQL1 or WRN may play an important role in the enhancement of DNA strand displacement, such as that occurring during lagging strand DNA synthesis at the replication fork, or during the DNA repair (for example, long patch base excision repair) that potentially leads to strand displacement. It has to be taken into account that the actual contribution of EXO1 in humans remains understudied and there is much scope for further work in this area
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