Correspondence To: Sikder M. Asaduzzaman, Tissue Banking and Biomaterial Research Unit, Atomic Energy Research Establishment, 1349 Dhaka, Bangladesh. E-mail: sikderasad@yahoo.com Bioscience and Bioengineering Communications Journal Homepage: www.bioscibioeng.com Mini Review Conversation between Mitochondria and Nucleus: Role of FEN1 and ING1 in Association with the Ringmaster PCNA Md. Shaifur Rahman 1 , Hossen M. Jamil 1 , Naznin Akhtar 1 , SM Abdul-Awal 2 and Sikder M. Asaduzzaman 1 1 Tissue Banking and Biomaterial Research Unit, Atomic Energy Research Establishment, 1349 Dhaka, Bangladesh 2 Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna 9208, Bangladesh Received: 20 June 2016; Received in Revised form: 29 June 2016; Accepted: 15 July 2016 Available online: 23 July 2016 Abstract Mitochondria and nucleus maintain collaboration during apoptosis and oncogenesis where two machineries FEN1 and ING1 are playing major role in the theatre of DNA metabolic pathway in concomitant with the metabolic actor PCNA. PCNA, FEN1 and ING1 localized in mitochondria and nucleus by forming a larger protein complex, potentially involved in the regulation of DNA damage repair, apoptosis and cancer. But the mechanism of these proteins migration and coordination between mitochondria and nucleus is unknown. Understanding the signaling across sub-cellular location based on FEN1/ING1/PCNA might lead to interlink the molecular regulation of cell death and immortalization within the mitochondrial and nuclear location. Keywords: Mitochondria, Nucleus, Apoptosis, FEN1, ING1, PCNA. 1. Introduction Maintenance of nuclear and mitochondrial genome integrity is critical to multicellular organisms. Nucleus and mitochondria are prime location where a growing number of DNA transacting proteins are found respond to a variety of environmental and cellular stresses. Oncogenesis, ageing and cell death can disrupt the genome either directly by causing DNA damage or indirectly through disruption of normal cellular processes that involve DNA. Critical to the process of maintaining genome integrity in higher organisms are the FEN1, ING1 and PCNA those serves to integrate signals. FEN1 is found in the nucleus and the shortened form of FEN1, FENMIT, localizes to mitochondria to maintain mtDNA integrity [Kazak et al. 2013; Kalifa et al, 2009; Liu et al. 2008; Szczesny et al. 2008]. FEN1 works nucleus in response to DNA damage and during S-phase of the cell cycle [Zheng et al. 2010]. ING1, an interacting partner of FEN1, translocates to the mitochondria in response to apoptosis inducing stimuli, independent of the cellular p53 pathway. The ability of ING1 to induce apoptosis in various cancer correlates well with its degree of translocation to the mitochondria after UV treatment [Bose et al. 2013]. ING1 translocate into the nucleolus as a binding partner that interacts with a nucleolar protein CSIG, functions as a novel pro-apoptotic regulator in response to DNA damage [Li et al. 2012]. Moreover, ING1 is localized in the cell nucleus and associated with chromatin modifying enzymes, linking tumor suppression directly Biosci Bioeng Commun 2016; 2(2): 118-122 eISSN 2414-1453 FEN1:Flap endonuclease-1; ING1: Inhibitor of growth 1; PCNA: Proliferating cell nuclear antigen; nDNA: Nuclear DNA; mtDNA: Mitochondrial DNA; EXO: Exonuclease; GEN: Gap endonuclease; BER: Base excision repair; NER: Nucleotide excision repair ROS: Reactive Oxygen Species; SP: Short patch; LP: Long patch; Polδ: DNA polymerase δ; dsDNA: Double strand DNA; RFC: Replication factor C; ssDNA: Single strand DNA; WRN: Werner protein; TNR: Trinucleotide repeat; PHD: Plant homeodomain; NLS: Nuclear localization signal; PIP: PCNA-interacting protein; UV: Ultraviolet; FENMIT: FEN1, localizes to mitochondria, mitochondrial targeting; CSIG: Cellular senescence-inhibited gene.