Characterization of DNA double-strand break repair pathways in diffuse large B cell lymphoma

Gopalakrishnan, Vidya and Dahal, Sumedha and Radha, Gudapureddy and Sharma, Shivangi and Raghavan, Sathees C and Choudhary, Bibha (2019) Characterization of DNA double-strand break repair pathways in diffuse large B cell lymphoma. In: MOLECULAR CARCINOGENESIS, 58 (2). pp. 219-233.

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Abstract

Efficient DNA repair is indispensable for maintaining genomic integrity in humans. Cancer associated deletions and mutations are mainly due to misrepaired DNA double-strand breaks (DSBs). Classical nonhomologous end joining (c-NHEJ) and homologous recombination (HR) are two major DSB repair pathways in humans. An error prone, alternative NHEJ pathway that utilizes microhomology was also reported in cancer cells and to a lesser extent in normal cells. In the present study, we evaluated the efficiency of various DSB repair pathways in the most common lymphoma, the diffuse large B cell lymphoma (DLBCL). Here we show that DNA repair through c-NHEJ pathway is limited in SUDHL8, a cell line derived from a DLBCL patient. Unlike c-NHEJ, microhomology mediated end joining (MMEJ) was predominant at physiological temperature. Consistent with the observation, expression level of repair proteins such as LIGASE I, LIGASE III, PARP1, CtIP, and MRE11 was higher in DLBCL cells when compared to c-NHEJ proteins. Further, inhibition of LIGASE I or MRE11, led to reduction in the efficiency of MMEJ in DLBCL cells. Besides, HR-mediated DSB repair occurring through gene conversion was observed. Thus, our results reveal the predominance of MMEJ over c-NHEJ in repairing DSBs in DLBCL cells, while error-free repair through HR was also evident.

Item Type:	Journal Article
Publication:	MOLECULAR CARCINOGENESIS
Publisher:	WILEY
Additional Information:	Copyright of this article belongs to WILEY
Keywords:	alternative NHEJ; classical NHEJ; DLBCL; DNA damage; double-strand breaks; genomic instability
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	29 Jan 2019 06:07
Last Modified:	29 Jan 2019 06:07
URI:	http://eprints.iisc.ac.in/id/eprint/61521

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