Ask about this productRelated genes to: XRCC1 protein
- Gene:
- BRCA2 NIH gene
- Name:
- BRCA2 DNA repair associated
- Previous symbol:
- FANCD1, FACD, FANCD
- Synonyms:
- FAD, FAD1, BRCC2, XRCC11
- Chromosome:
- 13q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1994-10-17
- Date modifiied:
- 2019-04-23
- Gene:
- XRCC1 NIH gene
- Name:
- X-ray repair cross complementing 1
- Previous symbol:
- RCC
- Synonyms:
- -
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2019-04-23
Related products to: XRCC1 protein
Related articles to: XRCC1 protein
- Emerging evidence has indicated possible efficacy benefit of platinum-based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple-negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results. - Source: PubMed
Zhao ZhenhuiLi LiHe MeiLi YanMa XiaopingZhao Bing - DNA repair genes are among the low-penetrance genes implicated in breast cancer. However variants of DNA repair genes may alter their protein function thus leading to carcinogenesis. Breast cancer is the most common cancer among women in India. The aim of the present study was to identify association, if any, of single nucleotide polymorphisms (SNP's) in four genes involved in DNA repair pathways including, rs1801320, rs25487, rs3218536, and rs861539 with the risk of breast cancer. In this case-control study 611 female subjects (311 breast cancer patients and 300 healthy controls) were screened for four SNPs using polymerase chain reaction-restriction fragment length polymorphism analyses. Multifactor dimensionality reduction (MDR) analysis was performed to estimate the gene-gene interaction. Protein-protein interaction network analysis were studied using the STRING database. The GC genotype ( = 0.018) and the combined GC+CC ( = 0.03) genotypes of rs1801320 were significantly associated with reduced risk of breast cancer. The CT genotype ( = 0.0001), the combined CT+TT genotypes ( = 0.0002), and the T allele ( = 0.0019) of rs861539 polymorphism were associated with reduced risk of the breast cancer. No association of rs25487 and rs3218536 polymorphisms with breast cancer was observed. MDR analysis indicated a positive interaction between and . String network analysis showed that the RAD51, XRCC1, XRCC2, and XRCC3 proteins are in strong interaction with each other and other breast cancer-related proteins such as BRCA2. rs1801320 and rs861539 polymorphisms were associated with reduced risk of breast cancer. There is evidence of positive interactions among , , , and . - Source: PubMed
Gupta PriyankaSambyal VasudhaGuleria KamleshUppal Manjit SinghSudan Meena - Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer. Neoadjuvant chemotherapy (NACT) has become standard therapy for local advanced breast cancer (LABC). The aim of our study was to investigate plasma ctDNA as a prognostic marker for outcome in patients with LABC treated with NACT. A total of 56 patients with LABC were involved in this study. ctDNA mutations were investigated by using a 100 gene panel-target capture next-generation sequencing. The patients then received standard NACT therapy: adriamycin and cyclophosphamide and paclitaxel (AC-T) or AC-TH (AC-T+ Trastuzumab) regimen. The efficacy of NACT was evaluated by Miller-Payne grading system. A predictive and weight model was used to screen ctDNA point mutation biomarkers for NACT. The ctDNA mutational profile of LABC patients was identified. For nonsynonymous mutations, the top 5 mutated genes were MTHFR (51/56, 91.1%), XPC (50/56, 89.3%), ABCB1 (48/51, 94.1%), BRCA2 (38/56, 67.9%), and XRCC1 (38/56, 67.9%). In addition, the mutation frequencies of PIK3CA and TP53 were 32.1% (18/56) and 26.8% (15/56), respectively. The predictive model indicated that XRCC1 44055726 (TG>-) mutation (25/56, 44.6%) was significantly associated with Miller-Payne 4-5 and Miller-Payne 3-5 responses. While mTOR 11249132(G>C) mutation (23/56, 41.1%) was associated with Miller-Payne 1-4 or Miller-Payne 1-3 responses. Furthermore, XRCC1 44055726 (TG>-) accompanied by mTOR wild type predicted a good NACT efficacy in all response classification systems. The ROC curves to discriminate good neoadjuvant chemotherapy efficiency (Miller-Payne 4-5) and poor efficiency (Miller-Payne 1-3) were created, and AUC value was 0.77. Our results suggested that ctDNA mutation of XRCC1 44055726 (TG>-) might be a positive biomarker for NACT therapy in LABC, while mTOR 11249132(G>C) mutation was potentially associated with NACT resistance. - Source: PubMed
Wei BenjieShan YanhongDu ZhaoliYin ChunxiaZhang QianqianLin HaifengZhang GuirongSong DongZuo Hongbin - The MRE11-RAD50-NBS1 (MRN) complex is critical for genomic stability. Although germline mutations in MRN may increase breast cancer susceptibility, such mutations are extremely rare. Here, we have conducted a comprehensive clinicopathological study of MRN in sporadic breast cancers. We have protein expression profiled for MRN and a panel of DNA repair factors involved in double-strand break repair (BRCA1, BRCA2, ATM, CHK2, ATR, Chk1, pChk1, RAD51, γH2AX, RPA1, RPA2, DNA-PKcs), RECQ DNA helicases (BLM, WRN, RECQ1, RECQL4, RECQ5), nucleotide excision repair (ERCC1) and base excision repair (SMUG1, APE1, FEN1, PARP1, XRCC1, Pol β) in 1650 clinical breast cancers. The prognostic significance of MRE11, RAD50 and NBS1 transcripts and their microRNA regulators (hsa-miR-494 and hsa-miR-99b) were evaluated in large clinical datasets. Expression of MRN components was analysed in The Cancer Genome Atlas breast cancer cohort. We show that low nuclear MRN is linked to aggressive histopathological phenotypes such as high tumour grade, high mitotic index, oestrogen receptor- and high-risk Nottingham Prognostic Index. In univariate analysis, low nuclear MRE11 and low nuclear RAD50 were associated with poor survival. In multivariate analysis, low nuclear RAD50 remained independently linked with adverse clinical outcomes. Low RAD50 transcripts were also linked with reduced survival. In contrast, overexpression of hsa-miR-494 and hsa-miR-99b microRNAs was associated with poor survival. We observed large-scale genome-wide alterations in MRN-deficient tumours contributing to aggressive behaviour. We conclude that MRN status may be a useful tool to stratify tumours for precision medicine strategies. - Source: PubMed
Publication date: 2021/11/15
Alblihy AdelShoqafi AhmedToss Michael SAlgethami MashaelHarris Anna EJeyapalan Jennie NAbdel-Fatah TarekServante JulietteChan Stephen Y TGreen AndrewMongan Nigel PRakha Emad AMadhusudan Srinivasan - A systematic knowledge of the roles of DNA repair genes at the level of the organism has been limited due to the lack of appropriate experimental approaches using animal model systems. Zebrafish has become a powerful vertebrate genetic model system with availability due to the ease of genome editing and large-scale phenotype screening. Here, we generated zebrafish mutants for 32 DNA repair and replication genes through multiplexed CRISPR/Cas9-mediated mutagenesis. Large-scale phenotypic characterization of our mutant collection revealed that three genes (atad5a, ddb1, pcna) are essential for proper embryonic development and hematopoiesis; seven genes (apex1, atrip, ino80, mre11a, shfm1, telo2, wrn) are required for growth and development during juvenile stage and six genes (blm, brca2, fanci, rad51, rad54l, rtel1) play critical roles in sex development. Furthermore, mutation in six genes (atad5a, brca2, polk, rad51, shfm1, xrcc1) displayed hypersensitivity to DNA damage agents. Our zebrafish mutant collection provides a unique resource for understanding of the roles of DNA repair genes at the organismal level. - Source: PubMed
Publication date: 2021/07/08
Shin UnbeomNakhro KhriezhanuoOh Chang-KyuCarrington BlakeSong HeaInVarshney Gaurav KKim YeongjaeSong HyeminJeon SangeunRobbins GabrielleKim SanginYoon SuhyeonChoi Yong JunKim Yoo JungBurgess ShawnKang SukhyunSood RamanLee YoonsungMyung Kyungjae