Regional conformational flexibility couples substrate specificity and scissile phosphate diester selectivity in human flap endonuclease 1
نویسندگان
چکیده
منابع مشابه
Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1
Human flap endonuclease 1 (FEN1) and related structure-specific 5'nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5'nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-mo...
متن کاملCorrigendum: Phosphate steering by Flap Endonuclease 1 promotes 5′-flap specificity and incision to prevent genome instability
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 enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA bin...
متن کاملHuman RECQL5β stimulates flap endonuclease 1
Human RECQL5 is a member of the RecQ helicase family which is implicated in genome maintenance. Five human members of the family have been identified; three of them, BLM, WRN and RECQL4 are associated with elevated cancer risk. RECQL1 and RECQL5 have not been linked to any human disorder yet; cells devoid of RECQL1 and RECQL5 display increased chromosomal instability. Here, we report the physic...
متن کاملHuman RECQL 5 b stimulates flap endonuclease 1
Human RECQL5 is a member of the RecQ helicase family which is implicated in genome maintenance. Five human members of the family have been identified; three of them, BLM, WRN and RECQL4 are associated with elevated cancer risk. RECQL1 and RECQL5 have not been linked to any human disorder yet; cells devoid of RECQL1 and RECQL5 display increased chromosomal instability. Here, we report the physic...
متن کاملModeling of flap endonuclease interactions with DNA substrate.
Structure-specific 5' nucleases play an important role in DNA replication and repair uniquely recognizing an overlap flap DNA substrate and processing it into a DNA nick. However, in the absence of a high-resolution structure of the enzyme/DNA complex, the mechanism underlying this recognition and substrate specificity, which is key to the enzyme's function, remains unclear. Here, we propose a ...
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ژورنال
عنوان ژورنال: Nucleic Acids Research
سال: 2018
ISSN: 0305-1048,1362-4962
DOI: 10.1093/nar/gky293