研究探討PARP-1與FACT的交互作用

Abstract

PARP-1是一個參與在DNA修復、轉錄、複製、重組以及調節染色質結構的多弁鉬簿嚏C FACT是一個由FACTp140和SSRP1組成的核蛋白。FACT已知在轉錄染色質模板時扮演著延長因子角色。在過去的研究中顯示PARP-1和FACT存在同一個多重蛋白複合體中。而在我們的研究中，我們發現PARP-1和FACT間的交互作用。它們之間的交互作用主要是透過PARP-1與FACTp140作用而不是透過SSRP1。PARP-1 與FACT間的交互作用是有細胞週期性的，且其作用最好的時期是在S phase。此外，它們的交互作用也可以被 g-射線刺激增加。FACTp140會增強PARP-1的酵素活性。綜合而言，我們證明了FACT可以調節PARP-1的酵素活性，而這樣的調節對於PARP-1在DNA複製、轉錄以及DNA修復有一定的重要性。

Poly(ADP-ribose) polymerase-1 (PARP-1) is a multifunctional enzyme involving in DNA repair, transcription, replication, recombination and modulation of chromatin structure. FACT is a nuclear protein composed of FACTp140 and SSRP1 heterodimeric complex. FACT is a known chromatin-specific elongation factor required for transcription of chromatin templates. Previous studies have shown that PARP-1 and FACT exist in the same multiprotein complex. In this study the interaction between PARP-1 and the FACT was examined. PARP-1 interacts with FACT through FACTp140, not SSRP1. The interaction between PARP-1 and FACT is cell-cycle-dependent, peaks at S phase. The interaction is stimulated after g-irradiation. FACTp140 may stimulate the automodification activity of PARP-1. In conclusion, we demonstrate that FACT can regulate the enzyme activity of PARP-1, an event important for PARP-1’s function in replication, transcription and DNA repair.