The interaction of DNA mismatch repair proteins with human exonuclease I.

J Biol Chem

Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Published: August 2001

Exonucleolytic degradation of DNA is an essential part of many DNA metabolic processes including DNA mismatch repair (MMR) and recombination. Human exonuclease I (hExoI) is a member of a family of conserved 5' --> 3' exonucleases, which are implicated in these processes by genetic studies. Here, we demonstrate that hExoI binds strongly to hMLH1, and we describe interaction regions between hExoI and the MMR proteins hMSH2, hMSH3, and hMLH1. In addition, hExoI forms an immunoprecipitable complex with hMLH1/hPMS2 in vivo. The study of interaction regions suggests a biochemical mechanism of the involvement of hExoI as a downstream effector in MMR and/or DNA recombination.

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M102670200DOI Listing

Publication Analysis

Top Keywords

dna mismatch
8
mismatch repair
8
human exonuclease
8
interaction regions
8
hexoi
5
interaction dna
4
repair proteins
4
proteins human
4
exonuclease exonucleolytic
4
exonucleolytic degradation
4

Similar Publications

Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations in APC, TP53, and KRAS are common in CRC, indicating key roles for these genes in tumor development and progression. However, for certain tumors with low frequencies of these mutations that are defined by tumor location and molecular phenotypes, a carcinogenic mechanism dependent on BRAF mutations has been proposed.

View Article and Find Full Text PDF

Background: Neoadjuvant combination immunotherapy is a potential treatment option for patients with proficient mismatch repair/microsatellite stable colorectal cancer. Preoperative screening via endoscopy and imaging examinations could help identify patients who may potentially achieve a complete response after neoadjuvant combination immunotherapy. This study aims to evaluate the diagnostic accuracy of endoscopic and imaging examinations in predicting pathological complete response after neoadjuvant combination immunotherapy.

View Article and Find Full Text PDF

Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador.

NPJ Genom Med

January 2025

Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Lynch Syndrome (LS) is the most common form of hereditary CRC and it is caused by germline defects in the DNA-mismatch repair (MMR) pathway. It is of extreme importance for affected LS patients and their relatives to identify the germline causative alteration to provide intensified surveillance to those at risk and allow early diagnosis and cancer prevention.

View Article and Find Full Text PDF

Characterization of the genomic landscape in liver oligometastatic NSCLC.

BMC Cancer

January 2025

Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Objectives: Emerging data have shown that local treatment could provide clinical benefit for non-small cell lung cancer (NSCLC) patients with oligometastasis. Liver metastases have the worst prognosis in advanced NSCLC, but the genomic characteristics of liver oligometastasis remain unclear. The aim of our study was to elucidate the molecular features of liver oligometastatic NSCLC.

View Article and Find Full Text PDF

Purpose: Constitutional mismatch repair deficiency (CMMRD) is a genetic cancer predisposition syndrome among children and young adults. This study aimed to evaluate the frequency of CMMRD among patients with pediatric high-grade glioma (pHGG) in a single tertiary care center in Pakistan, a country with high consanguinity rates.

Patients And Methods: We reviewed the data of patients age <18 years with pHGG, anaplastic astrocytoma, and diffuse midline glioma (DMG) with CMMRD testing between 2016 and 2023.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!