title: Fission yeast Drp1 is an essential protein required for recovery from DNA damage and chromosome segregation.
abstract: DNA double strand breaks (DSBs) are the most critical types of DNA damage that can leads to chromosomal aberrations, genomic instability and cancer. Several genetic disorders such as Xeroderma pigmentosum are linked with defects in DNA repair. Human Rint1, a TIP1 domain containing protein is involved in membrane trafficking but its role in DNA damage response is elusive. In this study we characterized the role of Drp1 (damage responsive protein 1), a Rint1 family protein during DNA damage response in fission yeast. We identified that Drp1 is an essential protein and indispensable for survival and growth. Using in vitro random mutagenesis approach we isolated a temperature sensitive mutant allele of drp1 gene (drp1-654) that exhibits sensitivity to DNA damaging agents, in particular to alkylation damage and UV associated DNA damage. The drp1-654 mutant cells are also sensitive to double strand break inducing agent bleomycin. Genetic interaction studies identified that Rad50 and Drp1 act in the same pathway during DNA damage response and the physical interaction of Drp1 with Rad50 was unaffected in drp1-654 mutant at permissive as well as non permissive temperature. Furthermore Drp1 was found to be required for the recovery from MMS induced DNA damage. We also demonstrated that the Drp1 protein localized to nucleus and was required to maintain the chromosome stability.
authors.affiliation: Molecular and Structural Biology Division, CSIR - Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: Molecular and Structural Biology Division, CSIR - Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Nafees
authors.initials: N
authors.lastname: Ahamad
authors.affiliation: Molecular and Structural Biology Division, CSIR - Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: shakil_ahmed@cdri.res.in.
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000595:Amino Acid Sequence; D001761:Bleomycin / Q000494:pharmacology; D043171:Chromosomal Instability; D020090:Chromosome Segregation; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008969:Molecular Sequence Data; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D014466:Ultraviolet Rays
chemical_list: C480032:Rad50 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D001761:Bleomycin; D008741:Methyl Methanesulfonate
keywords: Chromosomes; DNA repair; Drp1; Rint1; S. pombe; rad50