creators_name: Gaurav, Sachin
creators_name: Ranjan, Rajiv Kumar
creators_name: Kuldeep, Jitendra
creators_name: Dhiman,  Kanika
creators_name: Mahapatra, Pinaki Prasad
creators_name: Ashish, .
creators_name: Siddiqi, Mohammad Imran
creators_name: Ahmed, Shakil
type: article
datestamp: 2021-02-01 04:09:08
lastmod: 2021-02-01 04:09:08
metadata_visibility: show
title: The N-terminus region of Drp1, a Rint1 family protein is essential for cell survival and its interaction with Rad50 protein in fission yeast S.pombe
ispublished: pub
subjects: QR
keywords: S.pombe;Drp1;Rint1;Rad50DNA; repair;SAXS analysis
note: The copyright of this article belongs to Elsevier Science.
abstract: Background: Defects in DNA repair pathway can lead to double-strand breaks leading to genomic instability. Earlier we have shown that S.pombe Drp1, a Rint1/Tip1 family protein is required for the recovery from DNA damage.

Methods: Various truncations of Drp1 protein were constructed and their role in DNA damage response and interaction with Rad50 protein has been studied by co-immunoprecipitation and pull-down assays.

Results: The structural and functional analysis of Drp1 protein revealed that the N-terminus region of Drp1 is indispensable for the survival. The C-terminus truncation mutants, drp1 Cid and drp1C24 exhibit temperature sensitive phenotype and are hypersensitive against DNA damaging agents with elevated level of Rad52-YFP foci at non-permissive temperature indicating the impairment for DNA damage repair pathway. The essential N-terminus region of Drp1 interacts with the C-terminus region of Rad50 and might be involved in influencing the MRN/X function. Small-angle X-ray (SAXS) analysis revealed three-domain like shapes in Drp1 protein while the C-terminus region of Rad50 exhibit unusual bulges. Computational docking studies revealed the amino acid residues at the C-terminus region of Rad50 that are involved in the interaction with the residues present at the Nterminal region of Drp1 indicating the importance of the N-terminal region of Drp1 protein.

Conclusions: We have identified the region of Drp1 and Rad50 proteins that are involved in the interaction and their role in the DNA damage response pathway has been analyzed.

General significance: The functional and structural aspects of fission yeast Drpl protein and its interaction with Rad50 have been elucidated.
date: 2021-01-02
date_type: published
publication: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
volume: 1865
number: 1
publisher: Elsevier Science
id_number: 10.1016/j.bbagen.2020.129739
refereed: TRUE
official_url: https://linkinghub.elsevier.com/retrieve/pii/S0304-4165(20)30250-6
citation:   Gaurav, Sachin and Ranjan, Rajiv Kumar and Kuldeep, Jitendra and Dhiman, Kanika and Mahapatra, Pinaki Prasad and Ashish, . and Siddiqi, Mohammad Imran and Ahmed, Shakil  (2021) The N-terminus region of Drp1, a Rint1 family protein is essential for cell survival and its interaction with Rad50 protein in fission yeast S.pombe.  BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1865 (1).