"Nature" solves two decades of immune mystery, prompting exposure of DNA error repair 'behind the scenes'

Antibodies are important weapons for the immune system to recognize and resist pathogens such as viruses and bacteria

A few days ago, two research teams from Canada and France published back-to-back papers in the top academic journal "Nature", pointing out that a previously "unknown" gene, FAM72A, played a key role in the formation of diverse antibodies

Not only that, the researchers found that the function of this gene is closely related to induced mutation (mutagenesis), so it is not only about antibodies, it will also provide us with new understanding of the mechanism of cancer occurrence and development

Previous studies have pointed out that an enzyme in the process of antibody production is key to introducing errors into DNA, activation-induced cytosine deaminase (AID), which catalyzes deoxygenation in DNA.

For the past two decades, the complete process by which AID works has puzzled scientists: Why doesn't DNA go the way of correct repair when the wrong base is introduced?

The two research teams used genome-wide CRISPR to screen for genes involved in the B cell-induced mutation process, looking for which genes, if missing, would affect the occurrence of mutations

Further mouse experiments showed that the FAM72A gene is indispensable in the induced mutation process driven by AID

On the contrary, the high expression of Fam72a promoted the occurrence of gene mutation

The study authors noted that FAM72A is not only expressed in B cells, but FAM72A overexpression has also been observed in many cancers, including gastrointestinal, breast, lung, liver and ovarian cancers, implying that it may also be promoting carcinogenesis.

The researchers say they will explore these possibilities in follow-up work

Note: The original text has been deleted

References:

[1] Yuqing Feng et al.

[2] Mélanie Rogier et al.

[3] Unsung gene is key to how antibodies develop: U of T study Retrieved Nov.