Role of Paralogue of XRCC4 and XLF in DNA Damage Repair and Cancer Development

Front Immunol. 2022 Mar 2:13:852453. doi: 10.3389/fimmu.2022.852453. eCollection 2022.

Abstract

Non-homologous end joining (cNHEJ) is a major pathway to repair double-strand breaks (DSBs) in DNA. Several core cNHEJ are involved in the progress of the repair such as KU70 and 80, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Artemis, X-ray repair cross-complementing protein 4 (XRCC4), DNA ligase IV, and XRCC4-like factor (XLF). Recent studies have added a number of new proteins during cNHEJ. One of the newly identified proteins is Paralogue of XRCC4 and XLF (PAXX), which acts as a scaffold that is required to stabilize the KU70/80 heterodimer at DSBs sites and promotes the assembly and/or stability of the cNHEJ machinery. PAXX plays an essential role in lymphocyte development in XLF-deficient background, while XLF/PAXX double-deficient mouse embryo died before birth. Emerging evidence also shows a connection between the expression levels of PAXX and cancer development in human patients, indicating a prognosis role of the protein. This review will summarize and discuss the function of PAXX in DSBs repair and its potential role in cancer development.

Keywords: DSBs; PAXX; XLF; XRCC4; cNHEJ; cancer; posttranslational modifications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA
  • DNA Breaks, Double-Stranded*
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • Humans
  • Mice
  • Neoplasms* / genetics

Substances

  • DNA-Binding Proteins
  • PAXX protein, human
  • XLF protein, mouse
  • XRCC4 protein, human
  • XRCC4 protein, mouse
  • DNA