biostudies-literatureUnknown11Bakshi DBreast cancer has replaced cervical cancer as being the most common and having the highest mortality among women in India. <i>ANKLE</i> gene is conserved among organisms during evolutionary succession and is a member of LEM family proteins in lower metazoans and is involved in critical functions in the nuclear architecture, gene expression and cell signaling. <i>ANKLE1</i> is the human orthologous of LEM-3 and is involved in DNA damage response and DNA repair. Whole Exome Sequencing (WES) of paired breast cancer samples was performed and <i>ANKLE1</i> was found to be a new possible hotspot for predisposition of breast cancer. The mass array genotyping for breast cancer variant rs2363956 further confirmed the <i>ANKLE1</i> association with the studied population of breast cancer. To elucidate the role of <i>ANKLE1</i> in DNA damage, it was knocked down in MCF-7 breast cancer cell line and the expression of γH2AX was assessed. <i>ANKLE1</i> knockdown cells displayed elevated levels of γ-H2AX foci in response to the cisplatin induced replication stress. The localization pattern of <i>ANKLE1</i> further emphasized the role of <i>ANKLE1</i> in DNA repair process. We observed that <i>ANKLE1</i> is required for maintaining genomic stability and plays a role in DNA damage and repair process. These findings provided a molecular basis for the suspected role of <i>ANKLE1</i> in human breast cancer and suggested an important role of this gene in controlling breast cancer development among women in India.Frontiers in genetics609758https://www.ebi.ac.uk/biostudies/studies/S-EPMC7873468biostudies-literature<i>ANKLE1</i> as New Hotspot Mutation for Breast Cancer in Indian Population and Has a Role in DNA Damage and Repair in Mammalian Cells.PMC7873468Verma SSharma BKatoch AGoswami AShah RVaishnavi SBakshi DChakraborty SNagpal ABhat ABhat GRKumar Rfalse<i>ANKLE1</i> as New Hotspot Mutation for Breast Cancer in Indian Population and Has a Role in DNA Damage and Repair in Mammalian Cells.Breast cancer has replaced cervical cancer as being the most common and having the highest mortality among women in India. <i>ANKLE</i> gene is conserved among organisms during evolutionary succession and is a member of LEM family proteins in lower metazoans and is involved in critical functions in the nuclear architecture, gene expression and cell signaling. <i>ANKLE1</i> is the human orthologous of LEM-3 and is involved in DNA damage response and DNA repair. Whole Exome Sequencing (WES) of paired breast cancer samples was performed and <i>ANKLE1</i> was found to be a new possible hotspot for predisposition of breast cancer. The mass array genotyping for breast cancer variant rs2363956 further confirmed the <i>ANKLE1</i> association with the studied population of breast cancer. To elucidate the role of <i>ANKLE1</i> in DNA damage, it was knocked down in MCF-7 breast cancer cell line and the expression of γH2AX was assessed. <i>ANKLE1</i> knockdown cells displayed elevated levels of γ-H2AX foci in response to the cisplatin induced replication stress. The localization pattern of <i>ANKLE1</i> further emphasized the role of <i>ANKLE1</i> in DNA repair process. We observed that <i>ANKLE1</i> is required for maintaining genomic stability and plays a role in DNA damage and repair process. These findings provided a molecular basis for the suspected role of <i>ANKLE1</i> in human breast cancer and suggested an important role of this gene in controlling breast cancer development among women in India.2020-01-01T00:00:00Z20202026-05-02T13:19:44.052Z2021-02-21T10:44:12ZS-EPMC78734683358480810.3389/fgene.2020.609758