TY  - JOUR
N1  - The copyright of this article belongs to Elsevier Science.
ID  - open2647
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0304-4165(20)30250-6
IS  - 1
A1  - Gaurav, Sachin
A1  - Ranjan, Rajiv Kumar
A1  - Kuldeep, Jitendra
A1  - Dhiman,  Kanika
A1  - Mahapatra, Pinaki Prasad
A1  - Ashish, .
A1  - Siddiqi, Mohammad Imran
A1  - Ahmed, Shakil
Y1  - 2021/01/02/
N2  - 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.
PB  - Elsevier Science
JF  - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
VL  - 1865
KW  - S.pombe;Drp1;Rint1;Rad50DNA; repair;SAXS analysis
TI  - 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
ER  -