Phosphate steering by Flap Endonuclease 1 promotes 5′-flap specificity and incision to prevent genome instability

• Published in: Nature communications Vol. 8; no. 1; pp. 15855 - 15
• Main Authors: Tsutakawa, Susan E., Thompson, Mark J., Arvai, Andrew S., Neil, Alexander J., Shaw, Steven J., Algasaier, Sana I., Kim, Jane C., Finger, L. David, Jardine, Emma, Gotham, Victoria J.B., Sarker, Altaf H., Her, Mai Z., Rashid, Fahad, Hamdan, Samir M., Mirkin, Sergei M., Grasby, Jane A., Tainer, John A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.06.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 60 APPLIED LIFE SCIENCES; 631/208/211; 631/45/147; 631/45/173; 631/535/1266; Amino Acid Sequence; BASIC BIOLOGICAL SCIENCES; Binding Sites; Biochemistry; Catalysis; Catalytic Domain; Crystallography; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA biosynthesis; DNA Repair; DNA Replication; Electrostatic properties; Endonuclease; FEN1 protein; Flap Endonucleases - chemistry; Flap Endonucleases - genetics; Flap Endonucleases - metabolism; Flaps; Genomes; Genomic Instability; Humanities and Social Sciences; Humans; In vitro methods and tests; Integrity; multidisciplinary; Mutation; Phosphate; Phosphates - chemistry; Phosphates - metabolism; Polarity; Replication; Residues; Science; Science (multidisciplinary); Sequence Alignment; Stability; Steering; Substrate Specificity

DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 5′-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 5′-flap was enigmat...