title: Kaposi sarcoma herpes virus latency associated nuclear antigen protein release the G2/M cell cycle blocks by modulating ATM/ATR mediated checkpoint pathway.
abstract: The Kaposi's sarcoma-associated herpesvirus infects the human population and maintains latency stage of viral life cycle in a variety of cell types including cells of epithelial, mesenchymal and endothelial origin. The establishment of latent infection by KSHV requires the expression of an unique repertoire of genes among which latency associated nuclear antigen (LANA) plays a critical role in the replication of the viral genome. LANA regulates the transcription of a number of viral and cellular genes essential for the survival of the virus in the host cell. The present study demonstrates the disruption of the host G2/M cell cycle checkpoint regulation as an associated function of LANA. DNA profile of LANA expressing human B-cells demonstrated the ability of this nuclear antigen in relieving the drug (Nocodazole) induced G2/M checkpoint arrest. Caffeine suppressed nocodazole induced G2/M arrest indicating involvement of the ATM/ATR. Notably, we have also shown the direct interaction of LANA with Chk2, the ATM/ATR signalling effector and is responsible for the release of the G2/M cell cycle block.
authors: Division of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India.
authors: Amit
authors: A
authors: Kumar
authors: Division of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India.
authors: Sushil Kumar
authors: SK
authors: Sahu
authors: Division of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India.
authors: Suchitra
authors: S
authors: Mohanty
authors: Division of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India.
authors: Sudipta
authors: S
authors: Chakrabarti
authors: Division of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India.
authors: Santanu
authors: S
authors: Maji
authors: Division of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India.
authors: R Rajendra
authors: RR
authors: Reddy
authors: School of Biological Science, National Institute of Science Education and Research, Bhubaneswar, India.
authors: Asutosh K
authors: AK
authors: Jha
authors: School of Biological Science, National Institute of Science Education and Research, Bhubaneswar, India.
authors: Chandan
authors: C
authors: Goswami
authors: School of Biotechnology, KIIT University, Bhubaneswar, India.
authors: Chanakya N
authors: CN
authors: Kundu
authors: Department of Biotechnology, Regional Medical Research Centre for Tribals, Jabalpur, India.
authors: Shanmugam
authors: S
authors: Rajasubramaniam
authors: Department of Microbiology and Immunology, University of Nevada, Reno, School of Medicine, Reno, Nevada, United States of America.
authors: Subhash C
authors: SC
authors: Verma
authors: Division of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India; Department of Biotechnology, Siksha Vhabana, Visva Bharati, Santiniketan, Bolpur, India.
authors: Tathagata
authors: T
authors: Choudhuri
mesh_terms: D000956:Antigens, Viral / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016203:CDC2 Protein Kinase; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006566:Herpesviridae Infections / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000956:Antigens, Viral; D000970:Antineoplastic Agents; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C109540:latency-associated nuclear antigen; D064007:Ataxia Telangiectasia Mutated Proteins; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D015739:Nocodazole