Human RECQL5beta stimulates flap endonuclease 1

TY - JOUR

T1 - Human RECQL5beta stimulates flap endonuclease 1

AU - Speina, Elzbieta

AU - Dawut, Lale

AU - Hedayati, Mohammad

AU - Wang, Zhengming

AU - May, Alfred

AU - Schwendener, Sybille

AU - Janscak, Pavel

AU - Croteau, Deborah L

AU - Bohr, Vilhelm A

PY - 2010/1/16

Y1 - 2010/1/16

N2 - 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 physical and functional interaction of the large isomer of RECQL5, RECQL5β, with the human flap endonuclease 1, FEN1, which plays a critical role in DNA replication, recombination and repair. RECQL5β dramatically stimulates the rate of FEN1 cleavage of flap DNA substrates. Moreover, we show that RECQL5β and FEN1 interact physically and co-localize in the nucleus in response to DNA damage. Our findings, together with the previous literature on WRN, BLM and RECQL4's stimulation of FEN1, suggests that the ability of RecQ helicases to stimulate FEN1 may be a general feature of this class of enzymes. This could indicate a common role for the RecQ helicases in the processing of oxidative DNA damage.

AB - 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 physical and functional interaction of the large isomer of RECQL5, RECQL5β, with the human flap endonuclease 1, FEN1, which plays a critical role in DNA replication, recombination and repair. RECQL5β dramatically stimulates the rate of FEN1 cleavage of flap DNA substrates. Moreover, we show that RECQL5β and FEN1 interact physically and co-localize in the nucleus in response to DNA damage. Our findings, together with the previous literature on WRN, BLM and RECQL4's stimulation of FEN1, suggests that the ability of RecQ helicases to stimulate FEN1 may be a general feature of this class of enzymes. This could indicate a common role for the RecQ helicases in the processing of oxidative DNA damage.

KW - Cell Line

KW - Cell Nucleus

KW - DNA

KW - DNA Cleavage

KW - DNA, Single-Stranded

KW - Flap Endonucleases

KW - Humans

KW - RecQ Helicases

U2 - 10.1093/nar/gkp1217

DO - 10.1093/nar/gkp1217

M3 - Journal article

C2 - 20081208

SN - 0261-3166

VL - 38

SP - 2904

EP - 2916

JO - Nucleic Acids Symposium Series

JF - Nucleic Acids Symposium Series

IS - 9

ER -