title: Dynamics of replication proteins during lagging strand synthesis: A crossroads for genomic instability and cancer.
abstract: DNA replication is a complex phenomenon that requires the concerted action of several enzymes, together with their protein and non-protein cofactors. In the nucleus, the two DNA strands are duplicated by two completely independent methods due to their anti-parallel orientation and the restrictive nature of DNA polymerases that allow DNA synthesis in the 5'-3' direction only. In this review, we focus on the proteins that are involved in the more complex and discontinuous process of lagging strand DNA synthesis by the formation of small DNA fragments called Okazaki fragments which are later sealed to form a continuous strand of DNA. We try and connect all the protein-protein interactions important for lagging strand synthesis in the S-phase of the cell cycle, describe the dynamics of these interactions and go on to discuss the post-translational modifications that affect them. We also look at how mutations in any of the players of the lagging strand synthesis can cause genomic instability leading to cancer and discuss if any of the players may be targeted for cancer therapy.
authors.affiliation: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India.
authors.forename: Amit Laxmikant
authors.initials: AL
authors.lastname: Deshmukh
authors.affiliation: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India.
authors.forename: Chandan
authors.initials: C
authors.lastname: Kumar
authors.affiliation: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India.
authors.forename: Deependra Kumar
authors.initials: DK
authors.lastname: Singh
authors.affiliation: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Maurya
authors.affiliation: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India. Electronic address: d.banerjee@cdri.res.in.
authors.forename: Dibyendu
authors.initials: D
authors.lastname: Banerjee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004261:DNA Replication; D042822:Genomic Instability; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D009363:Neoplasm Proteins
keywords: DNA replication; Genomic instability; Lagging strand synthesis; Okazaki fragments; Protein-protein interaction