National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Nucleic Acids Res. 2010 May;38(9):2904-16. doi: 10.1093/nar/gkp1217. Epub 2010 Jan 16.
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, RECQL5beta, with the human flap endonuclease 1, FEN1, which plays a critical role in DNA replication, recombination and repair. RECQL5beta dramatically stimulates the rate of FEN1 cleavage of flap DNA substrates. Moreover, we show that RECQL5beta 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.
人类 RECQL5 是 RecQ 解旋酶家族的成员之一，该家族与基因组维护有关。已经鉴定出该家族的五个人类成员；其中三个，BLM、WRN 和 RECQL4 与癌症风险增加有关。RECQL1 和 RECQL5 尚未与任何人类疾病有关联；缺乏 RECQL1 和 RECQL5 的细胞显示出增加的染色体不稳定性。在这里，我们报告了 RECQL5 的大异构体 RECQL5beta 与人类 flap 内切酶 1（FEN1）的物理和功能相互作用，FEN1 在 DNA 复制、重组和修复中起着关键作用。RECQL5beta 极大地刺激了 FEN1 对 flap DNA 底物的切割速度。此外，我们表明 RECQL5beta 和 FEN1 物理相互作用，并在细胞核中响应 DNA 损伤而共定位。我们的发现，以及以前关于 WRN、BLM 和 RECQL4 刺激 FEN1 的文献，表明 RecQ 解旋酶刺激 FEN1 的能力可能是这类酶的一个普遍特征。这可能表明 RecQ 解旋酶在处理氧化 DNA 损伤方面具有共同作用。
